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INTRODUCTION — One of the strongest predictors of emotional well-being in cancer survivors, besides sexual function, appearance, and employability, is feeling healthy enough to be a good parent. Parenthood can represent normalcy, happiness, and life fulfillment. Cancer survivors are often fearful that their history of cancer or its treatment will have an adverse impact on offspring conceived after their cancer treatment, such as placing them at risk for malignancy, congenital anomalies, or impaired growth and development. They are also concerned about the risks of cancer recurrence, infertility, miscarriage, and achieving a successful pregnancy outcome.
Despite these concerns, surveys of female cancer survivors in California and Sweden reported that only about 50 percent recalled receiving reproductive health counseling [1,2]; the proportion is higher in male cancer survivors [2,3]. A subsequent study reported that receiving counseling about reproductive loss and the option to try to preserve fertility before treatment was important to survivors, even if they were unable to have children after chemotherapy . Others have noted that the rate of elective pregnancy termination among female cancer survivors was higher compared to sibling controls because of the fear that their prior cancer therapy would affect their children . Patient education regarding future reproductive function is thus an important component of the care of individuals with cancer .
Risk of infertility among cancer survivors — Infertility in cancer survivors can be caused by injury to the hypothalamic-pituitary-gonadal axis, as well as damage to the organs of the reproductive tract. Cytotoxic drugs, radiation therapy, surgery, and the disease process itself can all cause infertility, which may be temporary or permanent. The magnitude of risk depends on multiple factors, including:
●Type and stage of cancer
●Drug class and cumulative dose
●Radiation field, number of treatments, and cumulative dose
●Extent of surgical therapy
●Age (eg, prepubertal, postpubertal, near menopause)
The largest database on the risk of infertility in cancer survivors is the Childhood Cancer Survivor Study (CCSS), a cohort study of several thousand five-year cancer survivors from 26 Canadian and United States institutions who were younger than 21 years at the time of diagnosis (between January 1, 1970, and December 31, 1986) and who had an eligible malignancy: leukemia, central nervous system (CNS) cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms' tumor, neuroblastoma, soft-tissue sarcoma, or bone tumors. In a series of publications, fertility rates in female cancer survivors and female partners of male cancer survivors were compared to the rate in a sibling cohort [5-9]. Major findings were:
●The relative risk (RR) of a pregnancy among female survivors was lower than in female siblings (RR 0.81, 95% CI 0.73-0.90) . Poor prognostic factors included:
•Hypothalamic/pituitary radiation dose ≥30 Gy
•Ovarian/uterine radiation dose >5 Gy
•A summed alkylating agent dose score of three or four (the alkylating agent dose score was calculated by adding the tertile score [1, 2, or 3] for each of the alkylating agents given to a particular patient. Nonexposed patients had a score of 0).
●When only female survivors who received no or scatter (≤0.1 Gy) radiation to the ovaries were assessed, cancer survivors were as likely to report being pregnant as their siblings (hazard ratio [HR] 1.07, 95% CI 0.97-1.19) . Multivariable models showed a significant decrease in the pregnancy rates with hypothalamic/pituitary radiation doses ≥22 Gy compared with those receiving no hypothalamic/pituitary radiation therapy.
●Males who were not surgically sterile were less likely to father a pregnancy than siblings (HR 0.56, 95% CI -0.49 to 0.63) . Poor prognostic factors included:
•Radiation dose >7.5 Gy to the testes
•Higher cumulative alkylating agent dose score
●Female survivors had an increased risk of clinical infertility compared with their siblings (RR 1.48, 95% CI 1.23-1.78; >1 year of attempts at conception without success), which was most pronounced at early reproductive ages . Despite being equally likely to seek treatment for infertility, female survivors were less likely than their siblings to be prescribed drugs for treatment of infertility (RR 0.57, 95% CI 0.46-0.70). Risk factors for infertility included increasing doses of uterine radiation and alkylating agent chemotherapy. Although survivors had an increased time to pregnancy compared with their siblings, 64 percent of 455 participants with self-reported clinical infertility eventually achieved a pregnancy.
●Female survivors were at higher risk of nonsurgical premature menopause than siblings (8 versus 0.8 percent; RR 13.21, 95% CI 3.26-53.51) . Risk factors for nonsurgical premature menopause included:
•Exposure to increasing doses of radiation to the ovaries. Although the risk of nonsurgical premature menopause was most elevated among survivors exposed to the highest doses of ovarian irradiation (≥1000 cGy), exposure to doses as low as 1 to 99 cGy were associated with an increased risk of nonsurgical premature menopause compared with that in survivors who received no radiation.
•Increasing alkylating agent score (based on number of alkylating agents and cumulative dose). The risk for nonsurgical premature menopause was increased at all levels of exposure to alkylating agents and the risk increased with exposure to increasing quantities of alkylating agents. For survivors treated with both alkylating agents and abdominopelvic radiation, the cumulative risk of nonsurgical premature menopause approached 30 percent.
•A diagnosis of Hodgkin lymphoma.
For survivors who were treated with alkylating agents plus abdominopelvic radiation, the cumulative incidence of nonsurgical premature menopause approached 30 percent.
The risk of infertility in specific clinical settings is described in more detail separately, including but not limited to the following topics:
Pretreatment approaches to preservation of fertility — In both sexes, gonadal shielding from radiation therapy and limiting the extent of surgery, when possible, can help preserve fertility.
Several additional methods have been developed or are under investigation for fertility preservation in women. Cryopreservation of embryos or oocytes is a proven approach, while cryopreservation of ovarian tissue is considered investigational. In some cases, ovarian function can be preserved by transposition of gonads; auto-transplantation of gonadal tissue is an investigational procedure. The safety and efficacy of gonadotropin-releasing hormone (GnRH) agonists for prevention of ovarian toxicity is controversial and an active area of investigation.
The primary approach to fertility preservation in men is cryopreservation of sperm. Suppression of testicular function during chemotherapy by administration of GnRH agonists has not been successful.
These methods for preserving fertility in women and men are reviewed in detail separately. (See "Fertility preservation in patients undergoing gonadotoxic treatment or gonadal resection".)
Resources are available to offset the financial costs of these interventions (eg, LIVESTRONG Fertility).
Assessment of fertility potential after cancer therapy — The assessment of fertility potential after cancer therapy is challenging because fertility may be transiently impaired. Whether infertility is transient or permanent, and the duration of transient infertility, cannot be predicted reliably. Furthermore, the presence of functioning gonads does not reliably predict that pregnancy will occur.
Premenopausal women who have amenorrhea or irregular menstrual cycles should be evaluated for premature ovarian failure. The clinical manifestations are similar to those in women with spontaneous ovarian failure. However, in young women with amenorrhea after chemotherapy, diagnosis of premature ovarian failure can be problematic since ovarian dysfunction may not be permanent. (See "Clinical manifestations and evaluation of spontaneous primary ovarian insufficiency (premature ovarian failure)", section on 'Diagnosis'.)
Premenopausal women with regular menstrual cycles should undergo assessment of ovarian reserve. A low antimüllerian hormone (AMH) level may be the best test for prediction of diminished ovarian reserve in this population [10-13]. Data from a variety of infertility patients (including breast cancer survivors) planning in vitro fertilization (IVF) suggest that a low AMH level before the procedure is a useful marker for predicting women at risk for a poor response or no response to ovarian stimulation. (See "Evaluation of female infertility", section on 'Assessment of ovarian reserve'.)
In men, fertility potential is evaluated by semen analysis. If repeated semen analyses demonstrate severe oligozoospermia (less than 5 million spermatozoa/mL) or azoospermia, basal serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone should be measured. (See "Evaluation of male infertility".)
Risk of cancer recurrence — With the possible exception of gestational trophoblastic disease, pregnancy does not affect the risk of recurrence of any type of cancer. In particular, the risk of recurrent melanoma [14,15] or breast cancer [16-18] does not appear to be affected by a subsequent pregnancy. The optimal timing of pregnancy after conclusion of cancer treatment is uncertain and depends, in part, on patient-specific factors (eg, type of treatment, tumor type, prognosis). In general, as the highest risk for cancer recurrence is in the first two years after completing treatment, most authors suggest waiting this time period before attempting conception, after a thorough evaluation confirming cancer remission or cure. However, a pregnancy that occurs spontaneously within the first two years after completing cancer treatment does not suggest that cancer is more likely to recur. (See "Gestational breast cancer: Epidemiology and diagnosis" and "Tumor node metastasis (TNM) staging system and other prognostic factors in cutaneous melanoma".)
Treatment of infertility — The treatment of infertility after cancer therapy depends on the cause(s). Several factors may be contributing to infertility and some or all of these factors may have been present prior to therapy. Treatment is generally the same as that for patients without a history of cancer. Exceptions may include estrogen receptor positive breast cancer survivors and women treated with high-dose radiation involving the uterus. Women with estrogen-receptor positive breast cancer may benefit from ovulation induction with tamoxifen or aromatase inhibitors. Women with a history of uterine radiation are counseled that limited evidence suggests lower fecundity and an increased incidence of pregnancy complications after uterine radiation . (See "Overview of treatment of female infertility" and "Treatment of male infertility" and "Fertility preservation in patients undergoing gonadotoxic treatment or gonadal resection", section on 'Issues in women with breast cancer'.)
Female cancer survivors who elect in vitro fertilization (IVF) are counseled regarding the options of using autologous or donor oocytes. For female cancer survivors diagnosed within the five years prior to undergoing assisted reproductive techniques (ART), use of donor oocytes appears to result in higher live birth rates compared with autologous oocytes. In a population-based cohort study of women undergoing IVF with autologous oocytes within five years of entry into a cancer registry, women with prior cancer treatments (all types) had reductions of greater than 60 percent in pregnancy and live birth rates compared with women without cancer . Of the cancer survivors, the live birth rate varied from 54 percent for women with melanoma to 14 percent for women with breast cancer (the average live birth rate after IVF for women without cancer was 47 percent). In contrast, when women underwent IVF with donor oocytes, there were no differences in the pregnancy rates regardless of cancer treatment or cancer type. Once women with cancer became pregnant, their likelihood of having a live birth did not differ significantly from women without cancer whether donor or autologous oocytes were used. Of note, women who were diagnosed with breast cancer more than six months prior to ART had a live birth rate similar to the overall live birth rate for women with cancer (23.3 versus 24.7 percent). While more data are needed, this study suggests a negative effect of recent malignancy itself on ART success separate from the negative impact of chemotherapy on ovarian follicles.
Men with severe oligospermia may require IVF with intracytoplasmic sperm injection (ICSI). Men with azoospermia who did not bank sperm prior to chemotherapy/radiation may have some residual spermatogenesis, so evaluation and possible extraction of testicular sperm (TESE) may be appropriate. (See "Treatment of male infertility".)
PREGNANCY ISSUES — Available data on pregnancy and offspring outcomes among cancer survivors are generally reassuring. Limitations of most studies of this issue include retrospective study designs, inadequate adjustment for confounders, recall bias, small numbers of adverse events, loss to follow-up, misclassification and underreporting of some outcomes, and uncertain validity of data obtained from surveys and linked birth-cancer registries.
Pre-conception — Women with a history of cancer benefit from a consultation with a maternal-fetal medicine specialist to review their prior history, discuss the possible impact of treatment on pregnancy outcomes, assess the need for preconception testing (eg, echocardiogram), and plan for any additional antenatal monitoring that may be warranted.
Conception — In a retrospective cohort study from the Childhood Cancer Survivor Study (CCSS) that compared survivors of childhood cancer treated with chemotherapy only with their unaffected siblings, the survivors were somewhat less likely to conceive/father a pregnancy (38 versus 62 percent) or have at least one live birth (83 versus 90 percent) compared with their siblings . In multivariate analysis that compared male with female survivors, male survivors had a lower likelihood of pregnancy or live birth than female survivors (for pregnancy: hazard ratio [HR] 0.63 versus 0.87; for live birth: HR 0.36 versus 0.82). In male survivors, reduced likelihood of pregnancy was associated with upper tertile doses of cyclophosphamide, ifosfamide, procarbazine, and cisplatin. For female survivors, busulfan and lomustine (doses ≥411 mg/m2) were associated with decreased rates of pregnancy (HR 0.22 and 0.41, respectively).
Risk of congenital and chromosomal abnormalities — In studies including several thousand offspring, female cancer survivors and male cancer survivors who were treated for childhood cancer with chemotherapy, radiation therapy, or both had no increased risk of congenital anomalies, single gene disorders, or chromosomal syndromes in their offspring [22-31]. These studies primarily evaluated pregnancies that were conceived years after treatment. Some representative examples are illustrated below:
●The CCSS performed a retrospective cohort analysis of validated cases of congenital anomalies among 4699 children of 1128 male and 1627 female childhood cancer survivors . Chemotherapy with alkylating agents and radiotherapy doses to the testes and ovaries were quantified and related to risk of congenital anomalies using logistic regression. Major findings were:
•The overall prevalence of anomalies was 2.7 percent.
•The prevalence of anomalies was not increased among children whose mothers were exposed to radiation or alkylating agents (3.0 versus 3.5 percent in those with no exposure) nor among children of male survivors (1.9 versus 1.7 percent in those with no exposure).
•Neither ovarian radiation dose nor testicular radiation dose was related to risk of congenital anomalies.
●A case-control study using computerized record linkage determined the incidence of cancer in parents of children born with an anomaly versus a matched sample of parents of children without congenital anomalies . Over 170,000 mothers and fathers were included. The incidence of cancer was similar in the parents of anomalous and non-anomalous children. In addition, there was no association between congenital anomalies in offspring and any type of cancer treatment (eg, radiation therapy or chemotherapeutic treatment with an alkylating agent).
●An international study of over 25,000 survivors of childhood cancer in the United States and Denmark who gave birth to or fathered over 6000 children reported no significant difference in the incidence of genetic disease in children born to survivors and those born to sibling controls (3.7 and 4.1 percent, respectively, in the United States and 6.1 and 5.0 percent, respectively in Denmark) .
●The offspring of 1915 female survivors of childhood or adolescent cancer had a gender ratio (male:female) of 1.09:1.00 among their 4029 pregnancies . This figure is consistent with that in the general population and not significantly different from that for offspring of female siblings of the female survivors. This finding argues against transmission of lethal X-linked mutations as a result of cancer treatment. Similar findings have been reported by others .
In contrast to these generally reassuring studies, at least two studies have observed an increased risk of congenital anomalies in offspring of cancer survivors. One was a relatively small study of survivors of Wilms' tumor treated with radiation therapy that included only 20 malformed infants, suggesting chance may have accounted for the findings . The other was a population-based study from Sweden and Denmark restricted to offspring of male cancer survivors . In this study, offspring of male cancer survivors had a slightly but statistically higher rate of major congenital anomalies than offspring of fathers with no history of cancer (relative risk [RR] 1.17, 95% CI 1.05-1.31; absolute rate 3.7 versus 3.2 percent). One explanation for these findings, which are discordant with almost all previous studies, is that offspring of cancer survivors were examined more closely because of their paternal history, resulting in ascertainment bias.
Risk of miscarriage, preterm birth, growth restriction, stillbirth — The risk of adverse pregnancy outcomes (eg, miscarriage, preterm delivery, fetal growth restriction, stillbirth) in female cancer survivors depends, in part, on the type of therapy they received (chemotherapy, radiation therapy, surgery) and to non-treatment factors (eg, age at start of pregnancy, type and site of neoplasm). There is no strong evidence of an increased risk of adverse pregnancy outcome among female cancer survivors or female partners of male survivors who received chemotherapy for childhood cancer [4,26,33,35,36]. Chemotherapy does not appear to damage the uterus, which may account for the generally favorable pregnancy outcome in exposed patients . However, exposing the uterus to high doses of radiation can restrict uterine growth and cause vascular changes that impair uterine blood flow, which may lead to preterm birth, fetal growth restriction, and stillbirth [28,38-40].
Cervical surgery for treatment of cervical cancer can affect future risks of miscarriage and preterm delivery. (See "Fertility-sparing surgery for cervical cancer", section on 'Pregnancy outcome'.)
●Chemotherapy — In the CCSS, women who received chemotherapy alone or with other therapies (surgery, radiation therapy, or both) had lower rates of live birth than their female siblings (range RR 0.52 [chemotherapy alone] to 0.71 [chemotherapy, surgery, radiation therapy]) . This appeared to be due primarily to a higher rate of pregnancy termination, as the rates of miscarriage and stillbirth were generally statistically similar for the survivors and their siblings. In addition, the male:female sex ratio of 1.09:1.0 in offspring of female survivors was similar to that in the general population and in offspring of female siblings of the female survivors, suggesting exposure to mutagenic agents (chemotherapy, radiation therapy) did not increase transmission of lethal X-linked mutations. Lastly, the rate of live birth was not lower for patients treated with any particular drug compared with those not treated with that drug. The most frequently used chemotherapeutic drugs in this study were cyclophosphamide, doxorubicin, vincristine, dactinomycin, and daunorubicin.
The same investigators also compared pregnancy outcomes in the partners of male survivors of childhood cancer with the outcomes in the partners of their male siblings . Although the proportion of pregnancies that resulted in a live birth was significantly lower for the partners of the male survivors than for the partners of the survivors’ siblings (RR 0.79, 95% CI 0.65-0.96), this was due, in part, to a higher rate of pregnancy termination among the partners of male survivors compared with partners of their siblings. The rate of miscarriage was generally similar in both groups, with a possibly higher risk for some individual chemotherapeutic agents, which may have been due to chance. The stillbirth rate and the birth weight distribution were similar in both groups. Interestingly, this study reported a male:female sex ratio of 1.00:1.03, which is lower than that in female cancer survivors and the general population. Possible explanations for this finding are chance and lower testosterone levels from exposure to chemotherapeutic agents [41,42]. It is hypothesized that sex proportions of mammalian offspring are partially controlled by hormone levels of both parents at the time of conception and low levels of testosterone are associated with a high proportion of daughters .
●Radiation therapy — The partners of men who receive testicular radiation do not appear to be at increased risk of adverse pregnancy outcome [28,44]. In contrast, girls and young women who undergo pelvic radiation are at risk of developing abnormalities of the pelvic vasculature, which may decrease uteroplacental perfusion; radiation-induced myometrial changes, such as fibrosis, which may decrease uterine elasticity, distensibility, and volume; and injury to the endometrium, which may prevent normal decidualization [45-51]. These changes may account for some adverse pregnancy outcomes (fetal growth restriction, preterm delivery, placenta accreta, stillbirth) that have been reported in pregnancies occurring after pelvic radiation [4,26,28,33,38,39,45-47,52-55]. The risk of these outcomes depends on the total radiation dose, site irradiated, and the woman's age at the time of irradiation (the prepubertal uterus is particularly vulnerable) [28,51,56,57]. Sex steroid replacement significantly increases uterine volume, endometrial thickness, and uterine blood flow [58,59].
•In the CCSS, compared with female survivors who did not receive any radiotherapy, female survivors who received high-dose radiotherapy to the flank/uterus (>500 cGy) were at significantly increased risk of preterm birth (50.0 versus 19.6 percent), low birth weight (36.2 versus 7.6 percent), and having a small for gestational age (SGA) infant (18.2 versus 7.8 percent) . These risks were also noted at lower uterine radiotherapy doses (starting at 50 cGy for preterm birth and at 250 cGy for low birth weight). In addition, uterine and ovarian irradiation significantly increased the risk of stillbirth and neonatal death at doses greater than 10 Gy (RR 9.1, 95% CI 3.4-24.6; 5/18 [18 percent]) . For girls treated before menarche, irradiation of the uterus and ovaries at doses as low as 1.00 to 2.49 Gy significantly increased the risk of stillbirth or neonatal death (RR 4.7, 95% CI 1.2-19.0; 3/69 [4 percent]).
•Large studies of survivors of Wilms' tumor have compared the pregnancy outcome of those who did or did not receive abdominal radiotherapy [33,40,52]. Women who received flank radiation therapy as part of the treatment for unilateral Wilms' tumor were at increased risk of pregnancy-induced hypertension, fetal malposition and premature labor, and the increase in risk correlated with higher doses of radiation .
Pregnancy after breast cancer — (See "Approach to the patient following treatment for breast cancer", section on 'Fertility and pregnancy after breast cancer'.)
Pregnancy management — There are no standards for antenatal monitoring of cancer survivors for potential pregnancy complications. Women who received radiation therapy appear to be at highest risk for adverse pregnancy outcome. Therefore, in addition to standard prenatal care and screening, the author obtains a sonogram at about 18 weeks of gestation in patients who were treated with pelvic radiation in order to evaluate the placenta, fetus, and uterus/cervix. Patients who received flank radiation may benefit from cervical length screening at their 18-week ultrasound, but patients exposed to radiation in other locations or to chemotherapy do not have an increased risk for spontaneous preterm labor. In addition, an ultrasound is obtained at about 28 weeks for fetal growth assessment in all patients with a history of radiation therapy at any location.
Breastfeeding after treatment for breast cancer need not be discouraged except from the irradiated breast. Most women who have undergone irradiation for breast cancer are able to produce milk on the affected side, but the amount of milk produced may be less than that in a non-irradiated breast, particularly if the lumpectomy site was close to the areolar complex or transected many ducts . Even when breast milk is produced, breastfeeding from the irradiated breast is not advised because mastitis will be difficult to treat if it occurs [61,62].
Cancer risk in offspring — An excess risk of cancer in offspring of cancer survivors has not been demonstrated [63,64], unless the parent’s tumor is a component of an inherited syndrome, such as retinoblastoma and the various cancers associated with the Li-Fraumeni syndrome. (See "Li-Fraumeni syndrome" and "Retinoblastoma: Clinical presentation, evaluation, and diagnosis".) Survivors of ovarian or breast cancer who are positive for BRCA1 or 2 mutation have a 50 percent chance of passing the mutation to their offspring. (See "Overview of hereditary breast and ovarian cancer syndromes".)
Other malignancies that are less well recognized as having a familial component (eg, brain tumors and acute leukemia) may also aggregate in the relatives of some families. If an underlying genetic predisposition for such tumors is suggested in these families, pedigree analysis of the survivors' family should be elicited. (See "Risk factors for brain tumors", section on 'Genetic factors' and "Pathogenesis of acute myeloid leukemia", section on 'Familial acute leukemia and myelodysplasia syndromes'.)
Patients with heritable cancers should be counseled about risk of the disease in their offspring. (See "Overview of cancer survivorship care for primary care and oncology providers", section on 'Genetic implications'.)
A genetics counselor can discuss options for prenatal diagnosis or preimplantation genetic diagnosis, if this is desired. (See "Preimplantation genetic diagnosis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient education: Preserving fertility after cancer treatment in children (The Basics)" and "Patient education: Preserving fertility after cancer treatment in men (The Basics)" and "Patient education: Preserving fertility after cancer treatment in women (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Cytotoxic drugs, radiation therapy, surgery, and the disease process itself can all cause infertility, which may be temporary or permanent. The magnitude of risk depends on multiple factors, including:
•Type and stage of cancer
•Drug class and cumulative dose
•Radiation field, number of treatments, and cumulative dose
•Extent of surgical therapy
•Age (eg, prepubertal, postpubertal, near menopause)
●In both sexes, gonadal shielding from radiation therapy and limiting the extent of surgery, when possible, can help preserve fertility. Cryopreservation of embryos or oocytes is a proven approach for fertility preservation, and ovarian function can sometimes be preserved by transposition of gonads. The primary approach to fertility preservation in men is cryopreservation of sperm. (See 'Pretreatment approaches to preservation of fertility' above.)
●The assessment of fertility potential after cancer therapy is challenging because fertility may be transiently impaired. Whether infertility is transient or permanent, and the duration of transient infertility, cannot be predicted reliably, and the presence of functioning gonads does not reliably predict that pregnancy will occur. Fertility potential is assessed in women with tests such as antimüllerian hormone (AMH) level and by semen analysis in men. (See 'Assessment of fertility potential after cancer therapy' above.)
●Infertility treatment is generally the same as that for patients without a history of cancer. Estrogen receptor positive breast cancer survivors are an exception; such patients may benefit from ovulation induction with tamoxifen or aromatase inhibitors. (See 'Treatment of infertility' above.) For female cancer survivors diagnosed within the five years prior to undergoing assisted reproductive techniques, the use of donor oocytes appears to result in higher live birth rates compared with autologous oocytes.
●Parents who have been treated for childhood cancer with chemotherapy, radiation therapy, or both are not at increased risk of having children with congenital or chromosomal anomalies. (See 'Risk of congenital and chromosomal abnormalities' above.)
●The available data do not support an adverse effect of prior chemotherapy on the risk of miscarriage, fetal demise, or birth weight. Pregnancy in women who have received prior pelvic irradiation appears to be associated with complications such as miscarriage, preterm labor and delivery, low birth weight, and placenta accreta (see 'Risk of miscarriage, preterm birth, growth restriction, stillbirth' above). The birth weights of the offspring after radiation of any location, including outside of the female pelvis, are statistically lower compared to the offspring of survivors treated only with chemotherapy.
●The offspring of cancer survivors are not at increased risk for cancer, unless the parent’s tumor was a component of an inherited syndrome. (See 'Cancer risk in offspring' above.)
●With the possible exception of gestational trophoblastic disease, pregnancy does not affect the risk of recurrence of any type of cancer. (See 'Risk of cancer recurrence' above.)
- Niemasik EE, Letourneau J, Dohan D, et al. Patient perceptions of reproductive health counseling at the time of cancer diagnosis: a qualitative study of female California cancer survivors. J Cancer Surviv 2012; 6:324.
- Armuand GM, Rodriguez-Wallberg KA, Wettergren L, et al. Sex differences in fertility-related information received by young adult cancer survivors. J Clin Oncol 2012; 30:2147.
- Letourneau JM, Ebbel EE, Katz PP, et al. Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer 2012; 118:1710.
- Green DM, Whitton JA, Stovall M, et al. Pregnancy outcome of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Am J Obstet Gynecol 2002; 187:1070.
- Green DM, Kawashima T, Stovall M, et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2010; 28:332.
- Green DM, Kawashima T, Stovall M, et al. Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 2009; 27:2677.
- Barton SE, Najita JS, Ginsburg ES, 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; 14:873.
- Green DM, Nolan VG, Kawashima T, et al. Decreased fertility among female childhood cancer survivors who received 22-27 Gy hypothalamic/pituitary irradiation: a report from the Childhood Cancer Survivor Study. Fertil Steril 2011; 95:1922.
- Sklar CA, Mertens AC, Mitby P, et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 2006; 98:890.
- Brougham MF, Crofton PM, Johnson EJ, et al. Anti-Müllerian hormone is a marker of gonadotoxicity in pre- and postpubertal girls treated for cancer: a prospective study. J Clin Endocrinol Metab 2012; 97:2059.
- Miyoshi Y, Ohta H, Namba N, et al. Low serum concentrations of anti-Müllerian hormone are common in 53 female childhood cancer survivors. Horm Res Paediatr 2013; 79:17.
- Lunsford AJ, Whelan K, McCormick K, McLaren JF. Antimüllerian hormone as a measure of reproductive function in female childhood cancer survivors. Fertil Steril 2014; 101:227.
- Charpentier AM, Chong AL, Gingras-Hill G, et al. Anti-Müllerian hormone screening to assess ovarian reserve among female survivors of childhood cancer. J Cancer Surviv 2014; 8:548.
- Reintgen DS, McCarty KS Jr, Vollmer R, et al. Malignant melanoma and pregnancy. Cancer 1985; 55:1340.
- Grin CM, Driscoll MS, Grant-Kels JM. The relationship of pregnancy, hormones, and melanoma. Semin Cutan Med Surg 1998; 17:167.
- Peters MV. The effect of pregnancy in breast cancer. In: Prognostic factors in breast cancer, Forrest APM, Kunkler PB (Eds) (Eds), Williams and Wilkins, Baltimore 1968. p.65.
- Velentgas P, Daling JR, Malone KE, et al. Pregnancy after breast carcinoma: outcomes and influence on mortality. Cancer 1999; 85:2424.
- Danforth DN Jr. How subsequent pregnancy affects outcome in women with a prior breast cancer. Oncology (Williston Park) 1991; 5:23.
- Teh WT, Stern C, Chander S, Hickey M. The impact of uterine radiation on subsequent fertility and pregnancy outcomes. Biomed Res Int 2014; 2014:482968.
- Luke B, Brown MB, Missmer SA, et al. Assisted reproductive technology use and outcomes among women with a history of cancer. Hum Reprod 2016; 31:183.
- Chow EJ, Stratton KL, Leisenring WM, et al. Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 2016; 17:567.
- Byrne J, Rasmussen SA, Steinhorn SC, et al. Genetic disease in offspring of long-term survivors of childhood and adolescent cancer. Am J Hum Genet 1998; 62:45.
- Li FP, Fine W, Jaffe N, et al. Offspring of patients treated for cancer in childhood. J Natl Cancer Inst 1979; 62:1193.
- Dodds L, Marrett LD, Tomkins DJ, et al. Case-control study of congenital anomalies in children of cancer patients. BMJ 1993; 307:164.
- Green DM, Fiorello A, Zevon MA, et al. Birth defects and childhood cancer in offspring of survivors of childhood cancer. Arch Pediatr Adolesc Med 1997; 151:379.
- Chiarelli AM, Marrett LD, Darlington GA. Pregnancy outcomes in females after treatment for childhood cancer. Epidemiology 2000; 11:161.
- Kenney LB, Nicholson HS, Brasseux C, et al. Birth defects in offspring of adult survivors of childhood acute lymphoblastic leukemia. A Childrens Cancer Group/National Institutes of Health Report. Cancer 1996; 78:169.
- Signorello LB, Mulvihill JJ, Green DM, et al. Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study. Lancet 2010; 376:624.
- Winther JF, Olsen JH, Wu H, et al. Genetic disease in the children of Danish survivors of childhood and adolescent cancer. J Clin Oncol 2012; 30:27.
- Signorello LB, Mulvihill JJ, Green DM, et al. Congenital anomalies in the children of cancer survivors: a report from the childhood cancer survivor study. J Clin Oncol 2012; 30:239.
- Boice JD Jr, Tawn EJ, Winther JF, et al. Genetic effects of radiotherapy for childhood cancer. Health Phys 2003; 85:65.
- Winther JF, Boice JD Jr, Thomsen BL, et al. Sex ratio among offspring of childhood cancer survivors treated with radiotherapy. Br J Cancer 2003; 88:382.
- Green DM, Peabody EM, Nan B, et al. Pregnancy outcome after treatment for Wilms tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol 2002; 20:2506.
- Ståhl O, Boyd HA, Giwercman A, et al. Risk of birth abnormalities in the offspring of men with a history of cancer: a cohort study using Danish and Swedish national registries. J Natl Cancer Inst 2011; 103:398.
- Green DM, Whitton JA, Stovall M, et al. Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2003; 21:716.
- Reulen RC, Zeegers MP, Wallace WH, et al. Pregnancy outcomes among adult survivors of childhood cancer in the British Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 2009; 18:2239.
- Critchley HO, Wallace WH. Impact of cancer treatment on uterine function. J Natl Cancer Inst Monogr 2005; :64.
- Sanders JE, Hawley J, Levy W, et al. Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood 1996; 87:3045.
- Signorello LB, Cohen SS, Bosetti C, et al. Female survivors of childhood cancer: preterm birth and low birth weight among their children. J Natl Cancer Inst 2006; 98:1453.
- Green DM, Lange JM, Peabody EM, et al. Pregnancy outcome after treatment for Wilms tumor: a report from the national Wilms tumor long-term follow-up study. J Clin Oncol 2010; 28:2824.
- James WH. Occupations associated with low offspring sex ratios. Am J Ind Med 1994; 25:607.
- Egeland GM, Sweeney MH, Fingerhut MA, et al. Total serum testosterone and gonadotropins in workers exposed to dioxin. Am J Epidemiol 1994; 139:272.
- James WH. Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels around the time of conception. J Endocrinol 2008; 198:3.
- Wo JY, Viswanathan AN. Impact of radiotherapy on fertility, pregnancy, and neonatal outcomes in female cancer patients. Int J Radiat Oncol Biol Phys 2009; 73:1304.
- Hawkins MM, Smith RA. Pregnancy outcomes in childhood cancer survivors: probable effects of abdominal irradiation. Int J Cancer 1989; 43:399.
- Pridjian G, Rich NE, Montag AG. Pregnancy hemoperitoneum and placenta percreta in a patient with previous pelvic irradiation and ovarian failure. Am J Obstet Gynecol 1990; 162:1205.
- Norwitz ER, Stern HM, Grier H, Lee-Parritz A. Placenta percreta and uterine rupture associated with prior whole body radiation therapy. Obstet Gynecol 2001; 98:929.
- Critchley HO, Bath LE, Wallace WH. Radiation damage to the uterus -- review of the effects of treatment of childhood cancer. Hum Fertil (Camb) 2002; 5:61.
- Smith RA, Hawkins MM. Pregnancies after childhood cancer. Br J Obstet Gynaecol 1989; 96:378.
- Watanabe T, Matsubara S, Saito Y, et al. Pregnant woman with an extremely small uterus due to pelvic irradiation in childhood. J Obstet Gynaecol Res 2012; 38:559.
- Larsen EC, Schmiegelow K, Rechnitzer C, et al. Radiotherapy at a young age reduces uterine volume of childhood cancer survivors. Acta Obstet Gynecol Scand 2004; 83:96.
- Li FP, Gimbrere K, Gelber RD, et al. Outcome of pregnancy in survivors of Wilms' tumor. JAMA 1987; 257:216.
- Holm K, Nysom K, Brocks V, et al. Ultrasound B-mode changes in the uterus and ovaries and Doppler changes in the uterus after total body irradiation and allogeneic bone marrow transplantation in childhood. Bone Marrow Transplant 1999; 23:259.
- Winther JF, Boice JD Jr, Svendsen AL, et al. Spontaneous abortion in a Danish population-based cohort of childhood cancer survivors. J Clin Oncol 2008; 26:4340.
- Lie Fong S, van den Heuvel-Eibrink MM, Eijkemans MJ, et al. Pregnancy outcome in female childhood cancer survivors. Hum Reprod 2010; 25:1206.
- Critchley HO, Wallace WH, Shalet SM, et al. Abdominal irradiation in childhood; the potential for pregnancy. Br J Obstet Gynaecol 1992; 99:392.
- Bath LE, Critchley HO, Chambers SE, et al. Ovarian and uterine characteristics after total body irradiation in childhood and adolescence: response to sex steroid replacement. Br J Obstet Gynaecol 1999; 106:1265.
- O'Donnell RL, Warner P, Lee RJ, et al. Physiological sex steroid replacement in premature ovarian failure: randomized crossover trial of effect on uterine volume, endometrial thickness and blood flow, compared with a standard regimen. Hum Reprod 2012; 27:1130.
- Krause MS, Johnson MS, Delaney AA, et al. Successful increase in uterine volume and subsequent pregnancy in a patient with a history of radiation and chemotherapy. Am J Obstet Gynecol 2014; 211:e1.
- Wobbes T. Effect of a breast saving procedure on lactation. Eur J Surg 1996; 162:419.
- Findlay PA, Gorrell CR, d'Angelo T, Glatstein E. Lactation after breast radiation. Int J Radiat Oncol Biol Phys 1988; 15:511.
- Higgins S, Haffty BG. Pregnancy and lactation after breast-conserving therapy for early stage breast cancer. Cancer 1994; 73:2175.
- Sankila R, Olsen JH, Anderson H, et al. Risk of cancer among offspring of childhood-cancer survivors. Association of the Nordic Cancer Registries and the Nordic Society of Paediatric Haematology and Oncology. N Engl J Med 1998; 338:1339.
- Mulvihill JJ, Myers MH, Connelly RR, et al. Cancer in offspring of long-term survivors of childhood and adolescent cancer. Lancet 1987; 2:813.