Attitudes Toward Fertility Preservation in Female ...

The Journal of Reproductive Medicine®

Attitudes Toward Fertility Preservation in Female Cancer Patients Kelly Loi, M.R.C.O.G., Matthew Lau, M.R.C.O.G., Seong Feei Loh, F.R.C.O.G., Yah Yuen Tan, M.R.C.S., Ga Sze Hong, M.R.C.S., Mei Yoke Chan, M.R.C.P., and Ah Moy Tan, F.R.C.P.

OBJECTIVE: To survey patient attitudes toward fertiliplaced on counseling the patient during the treatment ty preservation techniques in the case of infertility from planning process. (J Reprod Med 2010;55:411–416) cancer treatment. STUDY DESIGN: A crossKeywords: adolescent, sectional survey on adolesbreast cancer, fertility cent cancer patients (ACPs) preservation. For women facing upcoming aged 15–21 years and their cancer therapies, fertility Recent advances in cancer parents, as well as on breast cancer patients (BCPs). preservation is an important issue therapy have resulted in an increased number of RESULTS: A total of 69% of that needs to be discussed. long-term cancer surviACPs were aware of the vors. Over the past 25 problem of infertility. Howyears, the 5-year survival ever, only 31% recalled being rate for all female cancer survivors combined has spoken to about treatment effects on fertility. Parents improved from 56% to 64%.1 In particular, the 5were significantly more likely to have been spoken to (58% vs. 31%, p < 0.022) and tended to be more interestyear survival for breast cancer is approaching 90%. ed in fertility preservation. The groups were in agreeFor childhood cancers, the 5-year survival rate at all ment that cancer therapy should not be delayed. Of the cancer sites has improved from 56% to 75%. It has BCPs, 67% expressed substantial concern regarding inbeen estimated that by 2010, 1 in 250 young adults fertility. They were more likely to have been spoken to will be childhood cancer survivors.2 Quality of life and tended to be younger and nulliparous, although stais an important issue for cancer survivors, and fertistical significance was not reached. Again, most were tility after cancer treatment is often a concern.3 With unwilling to delay therapy. the recent success and advances made in fertility CONCLUSION: There is an interest in fertility preserpreservation for cancer patients, international vation amongst our patients, but the medical information guidelines now recommend that these options be received may influence, to a certain extent, the attitudes discussed with the patient.4,5 There is, however, a of the patients. Greater emphasis should therefore be scarcity of data regarding patient attitudes toward From the Departments of Reproductive Medicine, Breast Surgery, and Paediatric Oncology, KK Hospital, Singapore. Presented as a poster presentation at the Congress on Obstetrics, Gyaenecology and Infertility meeting in Beijing, November 12–15, 2009. Address correspondence to: Kelly Loi, M.R.C.O.G., Department of Reproductive Medicine, 100 Bukit Timah Road, Singapore 289899 ([email protected]). Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.

0024-7758/10/5509-10-0411/$18.00/0 © Journal of Reproductive Medicine®, Inc. The Journal of Reproductive Medicine®

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this issue. For female patients, currently, cryopreservation of embryos is the most established technique, requiring ovarian stimulation, oocyte retrieval, and in vitro fertilization, which takes ~2–5 weeks. This may not be practical for many cancer patients. It is also not suitable for those with estrogen-sensitive tumors or those without a partner. Cryopreservation of oocytes has been promoted as a possible strategy but also requires ovarian stimulation and is fraught with technical difficulties. Review of results

With the recent advances and successes in fertility preservation techniques, viable options are now available. indicates low success rates, at < 2% live birth rate per thawed oocyte.4 In most situations in which time is of the essence, cryopreservation of ovarian tissue may be a better strategy. This is also the only available option for prepubertal patients. However, this method involves surgery and is still largely experimental. We wanted to assess the level of interest in fertility preservation, particularly by ovarian tissue cryopreservation in our patients. A survey was therefore conducted in two groups of patients in whom ovarian tissue cryopreservation would be most relevant: (1) female adolescent cancer patients (ACPs) aged 15–21 years and their parents and (2) breast cancer patients (BCPs). The objective of the study was to explore the attitudes toward fertility preservation among our local, predominantly Asian, population and the information received by our patients from the medical staff on this issue. Materials and Methods We conducted a cross-sectional survey of a sample of ACPs seen in the KK Hospital Paediatric Oncology Clinic and BCPs seen in the KK Hospital Breast Cancer Clinic from March 2008 to December 2008. Female ACPs aged 10–21 years were asked to participate in the study if they were receiving treatment or had received treatment for a malignancy. Accompanying parents were also invited to answer a questionnaire. Female BCPs were invited to participate in the study if they were < 40 years old at


the time of survey and were receiving treatment or had received treatment for a malignancy. Patients with end-stage disease were excluded, to avoid emotional trauma, because the survey mainly focused on future goals. Treatment was defined as surgery, chemotherapy, radiation therapy, or any combination of these. The survey was approved by the KK Hospital Institutional Review Board (IRB). Patients who met the inclusion criteria were approached by a clinical coordinator at the oncology clinic during their routine clinic visit. No distinction was made between patients coming for therapy and those coming for follow-up care. Patients’ and parental attitudes regarding fertility and fertility preservation were assessed using a questionnaire. The main areas evaluated were: (1) Patients’ thoughts about future life as an adult in the case of adolescent patients and concern regarding future fertility in the case of breast cancer patients (2) Whether they had been counseled about how treatment might affect fertility (3) Their interest in research-based fertility preservation techniques (4) Their willingness to postpone cancer therapy. The questionnaire mainly consisted of several yes/no categorical questions. Female ACPs were asked whether they had thought about what life would be like as an adult and whether they were aware of the problem of infertility. BCPs were asked if they were concerned about fertility after cancer treatment and to score their concern from 0 (no concern at all) to 3 (very concerned). Both ACPs and BCPs were asked if their doctor had talked to them about the effect of cancer treatment on their fertility. Parents were asked similar questions. Interest in surgical fertility preservation and willingness to postpone cancer therapy were also evaluated. Statistical analysis was performed using the Statistical Package for the Social Sciences (v11.5, SPSS, Chicago, Illinois). Descriptive analysis was performed for all variables listed in Table I. Subset analysis was conducted to examine the adolescent subgroup aged 10–14 years vs. 15–21 years and BCPs who were concerned about fertility vs. those who were not. For categorical answers, the χ2 test was used. For continuous variables, the t-test was used. The McNemar test was used to evaluate any disagreement between the adolescent’s answer and their parents’ answers. A p value of < 0.05 was considered significant.

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Results Adolescent Cancer Patients There were 54 responses from female ACPs, and 38 parental responses were collected. Patients’ demographics and disease characteristics are found in Table I. Of the ACPs, 58% (31 of 53) had a diagnosis of leukemia. The diagnoses of the remainder are listed in Table I. Of the patients, 85% (46 of 54) were treated with chemotherapy or radiotherapy or both, whereas 35% (19 of 54) had at least one type of therapy that put them at risk for infertility. Of the pa-

Table I Patient Characteristics Female adolescent cancer patients Age, mean (range) (yr) 10–14 15–21 Diagnosis Leukemia Lymphoma Ovarian Brain Bone Neuroblastoma Wilms Age at diagnosis (yr) Treatment received Surgery Chemotherapy Radiotherapy >1 Modality Nationality Singaporean Indonesian Canadian Race Chinese Malay Indian Eurasian Other Marital status Single No. of children 0 ≥1 Irregular menstruation cycle Breast cancer patients Age, mean (range) (yr) Age at diagnosis, mean (range) (yr) Treatment received Surgery Chemotherapy Radiotherapy Chemotherapy ± radiotherapy >1 Modality

Value 14 (10–21) 31 23 31 8 5 4 3 1 1 9 (0–16) 17 45 10 20/54 51 2 1 38 9 4 1 1 54 53 1 5 of 33 (15%) Value 37.5 (29–40) 36.5 (29–40) 14 (77.8%) 11 (61%) 5 (27.8%) 12 (66.7%) 11 (61%)

Nationality Singaporean Indonesian Malaysian Philippines Race Chinese Malay Indian Filipino Other Occupation Clerical Construction Domestic worker Health care Hospitality Not working Professional/manager Highest level of education achieved Degree Diploma Secondary Primary Marital status Married Parity 0 1 2 Irregular menstruation cycle

15 1 1 1 10 5 1 1 1 3 1 1 1 1 6 5 6 5 6 1 11 9 1 7 4/17 (22.2%)

tients, 69% (34 of 49) had thought about future life as an adult, and 78% (39 of 50) were aware of the fact that some people were unable to conceive. A total of 31% (16 of 51) had been counseled in regard to the impact of oncology treatment on fertility. No statistically significant difference in primary outcome between the younger and older adolescent patients was found. The older group (24% vs. 11%) seemed to be more interested in fertility preservation treatment, although this comparison is not statistically significant (Table II). Agreements between adolescent and parental attitudes regarding outcomes are shown in Table II. Significantly more parents had been counseled about the treatment effect on their children’s fertility compared with their adolescent counterparts. There was otherwise no statistically significant disagreement between female adolescents and their parents on other questions (Table III). Breast Cancer Patients A total of 18 responses were collected from BCPs. Patients’ demographics and disease characteristics

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Table II Survey on Adolescent Cancer Patients Primary outcome on adolescent cancer patients Have you thought about the future life as an adult? Yes Do you know that some people are unable to have children? Yes Has anyone talked to you about how treatment might affect your/ your child’s fertility? Yes Would you be interested/encourage or allow your child in undergoing research-based fertility treatment techniques? Yes Would you still be interested if the techniques involved surgery? Yes Would you be willing to delay starting your/your child’s cancer therapy for 1 week or more? Yes

are found in Table I. Of these patients, 67% (12 of 18) were treated with chemotherapy, radiotherapy, or both, and 61% (11 of 18) had at least one type of cancer therapy. Of the 18 BCPs surveyed, 12 (72%) were substantially concerned about the treatment effect on fertility. Those who were concerned were more likely to have been spoken to, younger, and more likely to be nulliparous compared to those who were not concerned (Table IV). However, the differences did not reach statistical significance. Subgroup analysis showed that of those who were concerned about fertility, 83% (10 of 12) were counseled about the impact of cancer treatment on fertility compared to 50% (3 of 6) of the subgroup who were not concerned. Of the concerned group, 58% (7 of 12) were interested in undergoing research-based fertility treatment, with 50% (6 of 12) interested even if it involved surgery. However, only 33% (4 to 12) were willing to delay starting cancer therapy. Discussion Chemotherapy and radiotherapy pose significant risks to future fertility. With the recent advances and successes in fertility preservation techniques, viable options are now available.6 However, there

Table III

10–14 yr of age (%)

15–21 yr of age (%)

p Value

18/28 (64) 21/27 (77.8)

16/21 (76.2) 18/23 (78.3)

0.282 0.620

9/28 (32.1)

7/23 (30.4)

0.570

3/27 (11.1) 2/28 (7)

5/21 (23.8) 2/21 (9.5)

0.217 0.579

0/25

2/15 (13.3)

0.135

are few studies evaluating the knowledge and attitudes of patients toward fertility preservation.7,8 One of the few studies on this issue was published by Burns et al.9 They found that adolescents and adults do think of the future. Younger adolescents are just as likely to think of the future as older adolescents. Adolescents also had prior knowledge of infertility. Similarly, we also found that a large percentage of adolescents had thought about their future life as an adult. Adolescents also reported baseline knowledge on infertility, and an equal proportion of younger and older adolescents were aware of the problem of infertility. This supports the assertion that adolescents of all ages are capable of participating in a decision regarding fertility preservation, and therefore they should be involved in the discussion regarding preservation of fertility. Our study, however, found that significantly more parents were given counseling on fertility issues compared to the adolescents. This may have contributed to the apparent lower levels of interest in research-based fertility preservation in our adolescent population, with an average of 16% of adolescents and 30% of parents interested. Thus education and counseling on the subject could play an important role.

Agreement Between Parent and Adolescent Responses

Primary outcome on adolescent cancer patients Has anyone talked to you about how treatment might affect your/your child’s fertility? Yes Would you be interested/encourage or allow your child in undergoing research-based fertility treatment techniques? Yes Would you still be interested if the techniques involved surgery? Yes Would you be willing to delay starting your/your child’s cancer therapy for 1 wk or more? Yes

Parents’ answer on yes (%)

In agreement with adolescents (%)

McNemar p value

22/38 (58)

65

0.022

11/34 (32) 7/35 (20)

79 80

0.453 0.453

1/29 (3)

90

1

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Table IV Survey on Breast Cancer Patients How concerned are you about treatment effects on fertility? No. Total Para ≥1 (%) Age (median) Has anyone talked to you about how treatment might affect your fertility? Yes (%) Were your concerns addressed adequately by the doctor? Yes (%) Would you be interested in undergoing research-based fertility treatment techniques? Yes (%) Would you still be interested if the techniques involved surgery? Yes (%) Would you be willing to delay starting your cancer therapy for 1 wk or more? Yes

With regard to BCPs, a large percentage was substantially concerned about the treatment effects on their fertility. This is comparable with previous studies on BCPs.10 Of importance, more BCPs who were concerned about fertility after cancer treatment had recollection on fertility counseling compared to those who were not concerned (83% [11 of 13) vs. 50% [2 of 5]). The concerned subgroup also tended to be younger and nulliparous, so it may be postulated that counseling was biased toward this subgroup of patients. However, one could also argue that with good counseling before cancer treatment, greater awareness of the fertility issue could be instilled and therefore more BCPs would be concerned about their fertility. More than half of the BCPs who were concerned about fertility were interested in fertility preservation, even if it involves surgery. As with adolescents and their parents, most BCPs were not willing to delay their cancer therapy. One main limitation in our study is the small sample size. Therefore the result may not be applicable to the general population. Our study was intended as a pilot study to gather information on cancer patient attitudes in regard to fertility preservation. We also wanted to assess the feasibility of offering ovarian tissue cryopreservation to our patients. This would be the first pilot study addressing the issue in Singapore. Our study also focused only on two main target patient populations in whom ovarian tissue cryopreservation may be most relevant. The most common cancers in women of reproductive age in our population include Hodgkin’s and non-Hodgkin’s

0 (not at all)

1 (little concern)

2 (moderately concerned)

3 (very concerned)

5

1

6

6

p Value

6 4/6 (67) 38.2 (33–40)

12 4/12 (38) 35.6 (29–40)

0.201 0.126

3/6 (50) 4/6 (67)

10/12 (83) 10/12 (83)

0.153 0.453

0/6

7/12 (58)

0.015

0/6

6/12 (50)

0.035

0/6

4/12 (33)

0.201

lymphoma and breast cancer.11 We therefore chose to study ACPs in whom ovarian tissue cryopreservation would be the only available method. We also chose to study BCPs because many such patients may have estrogen-sensitive tumors and may be without a partner and unable to undergo in vitro fertilization and embryo cryopreservation. For women facing upcoming cancer therapies, fertility preservation is an important issue that needs to be discussed. Currently, fertility preservation techniques are performed as experimental procedures under IRB guidelines. Cancer survival in Singapore has improved remarkably with the advancement of medical and cancer treatment11; health care workers should be educated and made aware of the options available for fertility preservation with the aim of improving the quality of life of the cancer survivors. As a recent study indicated, most oncologists probably recognize the importance of discussing infertility risks but many may not discuss fertility preservation routinely.12 Increasing awareness through educational events may influence current practice patterns and increase collaboration between reproductive endocrinologists and oncologists. In conclusion, there is interest in fertility preservation among our patients, but most are unwilling to delay therapy for it. The results of the survey also indicate that the medical information received may influence, to a certain extent, the attitudes of our patients. Greater emphasis should therefore be placed on counseling on fertility preservation during the treatment planning process with the patient.

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