https://orcid.org/0000-0002-5988-5865
Abstract
What are the reproductive experiences and outcomes of people who store reproductive material before cancer treatment?
Of respondents who had tried to achieve pregnancy since completing cancer treatment almost all had succeeded, in most cases through natural conception.
People of reproductive age who are diagnosed with cancer can cryopreserve reproductive material to guard against the adverse effects on fertility of gonadotoxic treatment. Little is known about the reproductive outcomes of people who undergo fertility preservation before cancer treatment.
Cross-sectional survey.
Women and men who had stored reproductive material before cancer treatment at two private and one public fertility clinics up to June 2014 and were at least 18 years old at the time were identified from medical records and invited to complete an anonymous questionnaire about their reproductive experiences.
Of the 870 potential respondents 302 (171 female and 131 male) returned completed questionnaires yielding a response rate of 34.5% (39.5% and 29.7% for female and male respondents, respectively). Current age was similar for women and men (37.2 years) but men had been diagnosed with cancer significantly earlier in life than women (28.2 versus 30.3 years, P = 0.03). Almost two-thirds of respondents wished to have a child or another child in the future, some of whom knew that they were unable to. One in ten respondents was a parent before the cancer diagnosis and around one-third had had a child since diagnosis or was pregnant (or a partner in pregnancy) at the time of the survey. Of those who had tried to conceive since completing cancer treatment (N = 119) 84% (79% of women and 90% of men) had had a child or were pregnant (or a partner in pregnancy). Most of the pregnancies since the diagnosis of cancer occurred after natural conception (58/100, 58%). Of the 22 women (13% of all women) and 35 men (27% of all men) who had used their stored reproductive material four women (18%) and 28 men (80%) had had a child or were pregnant or a partner in pregnancy at the time of completing the survey. The most commonly stated reason for not using the stored material was not being ready to try for a baby.
The relatively low response rate, particularly among men, means that participation bias may have influenced the findings. As type of cancer was self-reported and we did not ask questions about respondents’ cancer treatments, it is not possible to link reproductive outcomes to type of cancer or cancer treatment. Also, there is no way of comparing the sample with the populations they were drawn from as data on reproductive outcomes of people who store reproductive material before cancer treatment are not collected routinely. This might have led to over- or underestimates of the reproductive experiences and outcomes reported in this paper.
The findings add to the limited evidence about the reproductive outcomes of this growing group of people and can be used to inform the advice given to those contemplating fertility preservation in the context of cancer.
The study was funded by the National Health and Medical Research Council (APP1042347). The authors have no conflicts of interest to declare.
Not applicable.
Introduction
Many of those diagnosed with cancer in their reproductive years have unfulfilled parenthood aspirations and hope to have children after treatment (Kirkman et al., 2013; Schmidt et al., 2014). However, cancer treatments can adversely affect both male and female fertility and reduce the chance of conception among survivors (Imbert et al., 2014; van der Kaaij et al., 2014). To guard against this, fertility preservation techniques have been developed and are offered by some assisted reproductive technology (ART) clinics. The need for fertility preservation is growing as increasing numbers of people survive cancer.
Depending on their circumstances, people facing cancer treatment in their reproductive years can be offered cryopreservation of sperm, oocyte, ovarian or testicular tissue, or embryos to increase the likelihood of having children in the future. Methods for freezing sperm have been successfully applied for many decades (Walters et al., 2009) whereas the science of preserving female fertility is more recent. Techniques for freezing oocytes developed in the 1990s have largely been replaced by vitrification, which is more efficient (Gook and Edgar, 2007; Cobo and Diaz, 2011). In the last few years freezing of ovarian and testicular tissue and subsequent re-implantation has shown some promising results (Onofre et al., 2016; Jadoul et al., 2017; Ladanyiet al., 2017). For women who are partnered freezing embryos before undergoing cancer treatment can be an option.
Clinical guidelines recommend that patients are made aware of the potential threat to fertility posed by cancer treatment as early as possible in the treatment process; that women and men facing cancer treatment are offered fertility preservation; and that advice to patients includes expected outcome of subsequent fertility treatment, and viability of thawed material (Loren et al., 2013; National Collaborating Centre for Women's and Children's Health, 2013; Peccatori et al., 2013; The Ethics Committee of the American Society for Reproductive, 2013). While information about the potential effects on fertility of cancer treatment and available options for fertility preservation are now commonly given to or discussed with patients (Kelvin et al., 2016), information about the viability of stored reproductive material and expected reproductive outcomes post chemotherapy is more difficult to provide because evidence about usage and outcomes from using cryopreserved material stored before cancer treatment is still very limited (Argyle et al., 2016; Kato, 2016). Follow-up studies to date indicate that utilization of stored material by women who freeze embryos or oocytes before cancer treatment is low and that most post-treatment pregnancies result from natural conception or ART with fresh oocytes. Of 39 women who stored embryos before cancer treatment over a 15-year period at a hospital in the UK, 5 (13%) returned for embryo transfer (of whom two had a live birth), 3 (8%) conceived naturally, 14 (36%) discarded their embryos and 22 (56%) had embryos remaining in storage (Barcroft et al., 2013). Of 68 women in The Netherlands who had stored oocytes for medical reasons on average 25 months earlier, 16 had since tried to conceive: 8 were trying to conceive naturally at the time of the study, 5 had conceived naturally and 3 had conceived with ART without the stored material (Dahhan et al., 2014). A review of 30 studies reporting reproductive outcomes for 11 798 men who had stored sperm before cancer treatment found that only 8% had returned to use it and of them about half achieved fatherhood (Ferrari et al., 2016).
To add to the limited existing evidence, the aim of this study was to describe the reproductive experiences and outcomes of people who had stored reproductive material before cancer treatment.
Materials and Methods
Ethics approval
The study was approved by the Human Research Ethics Committees of Monash University (CF13/3877–2013001994), Melbourne IVF (31/14-MIVF), Royal Women's Hospital (14/13) and Monash IVF (15154M).
Setting
In the state of Victoria, Australia, two large private ART centres (Melbourne IVF and Monash IVF) and a public hospital (Royal Women's Hospital) have been providing fertility preservation services for more than two decades. Together they undertake over 90% of all fertility preservation procedures in Victoria and have significant clinical and scientific expertise in this area. People who are diagnosed with cancer in their reproductive years can be referred to these clinics for counselling about fertility preservation options. Referral rates have increased over the two decades since fertility preservation was introduced and it is now expected that most oncologists in Victoria discuss fertility preservation with their adult patients before starting cancer treatment and refer those who wish to pursue this or wish to consult with a fertility specialist to one of the clinics (Hammarberg et al., 2017).
Participants
The study population was all people diagnosed with cancer who cryopreserved reproductive material at Melbourne IVF, the Royal Women's Hospital or Monash IVF to June 2014 when they were aged at least 18 years. Survivors, including those who had still had material stored and those who had used or discarded their material, were eligible to participate.
Data source
A study-specific questionnaire was developed by the researchers. It was informed by the published literature and the investigators’ extensive combined expertise in the clinical management, science, psychology and record keeping relating to fertility preservation. The questionnaire included questions with fixed response options about sociodemographic characteristics (sex, age at cancer diagnosis and currently, relationship status at cancer diagnosis and currently, and health insurance status); the type of cancer; the type of material stored (oocytes/ovarian tissue/sperm/testicular tissue/embryos) and year of storage; whether a doctor had been consulted about fertility since storing material (yes/no) and outcome of consultation (was told still fertile/not fertile but took no further steps/not fertile and sought help with conception/other); whether menstrual period patterns had changed since undergoing cancer treatment; whether the stored material had been used (yes/no); reasons for not using the stored material (multiple response options from a list); outcomes of using stored material (thawing unsuccessful, thawing successful but no embryos, embryos formed but no pregnancy, pregnancy loss, currently pregnant/live birth); reproductive experiences before and after storing material; whether material was still stored; and ideal and expected number of children. A copy of the questionnaire is available as Supplementary Material.
Procedure
The clinical services used their patient databases to identify potential respondents. Before making contact, the National Death Index was consulted to ensure that the family of a deceased person was not accidentally approached. In November 2014 those deemed eligible were sent a study-pack. It included a personalized, sensitively written letter signed by the treating clinician which described the purpose of the study and invited participation; detailed participant information which emphasized that participation was voluntary and responses anonymous; the questionnaire; and a return pre-paid envelope addressed to the researchers who were independent of clinical services. A reminder letter was sent from the clinics 3 weeks later, after which there were no further attempts at recruitment.
Data management and analysis
Data were entered into a password protected secure database and analysed in SPSS using descriptive statistics (IBM SPSS Statistics 20). Not all respondents answered all questions. Where there were missing data the number of responses are reported and percentages are proportions of those who provided a response.
Results
Response rate
Study packs were mailed to 933 people; 447 (48%) women and 486 (52%) men. Of these 63 were returned for the following reasons: unknown address (n = 14), material had been frozen for conditions other than cancer (n = 39), the person had died (n = 7), diagnosed with cancer after storing material (n = 1), had cancelled storage (n = 1) and was under the age of 18 at the time of storage (n = 1). Of the remaining 870 potential respondents 302 (171 female and 131 male) returned completed questionnaires yielding a response rate of 34.5% (39.5% and 29.7% for female and male respondents, respectively). One female respondent was a mother who had stored oocytes for her baby daughter who had been diagnosed with cancer and her data were excluded from analyses.
Characteristics of respondents
Respondents’ characteristics are shown in Table I. Current age was similar for women and men but men had been diagnosed with cancer significantly earlier in life than women (28.2 versus 30.3 years, P = 0.03). The three most common forms of cancer among female respondents were breast cancer (48%), lymphoma (24%) and reproductive system cancer (11%). Among male respondents they were reproductive system cancer (40%), lymphoma (38%) and brain cancer (8%). Among both women and men, more were married or co-habiting at the time of completing the questionnaire than at the time of the cancer diagnosis. Almost all male respondents had stored sperm; only five had stored testicular tissue. Approximately equal proportions of women reported storing oocytes, ovarian tissue and embryos. Some had stored more than one type of reproductive material.
Respondent characteristics (n = 301).
| Women | Men | All | |
|---|---|---|---|
| Age at cancer diagnosis mean (SD) | 30.3 (7.24) | 28.2 (9.21) | 29.4 (8.20) |
| Age at time of survey mean (SD) | 37.2 (7.05) | 37.2 (9.31) | 37.2 (8.10) |
| Relationship status at cancer diagnosis, n (%) | |||
| Single | 96 (56) | 85 (65) | 181 (60) |
| Married/co-habiting | 74 (44) | 45 (35) | 119 (40) |
| Relationship status at time of survey, n (%) | |||
| Single | 59 (35) | 50 (38) | 109 (36) |
| Married/co-habiting | 111 (65) | 80 (62) | 191 (64) |
| Year material stored, n (%) | |||
| 1995–1999 | 18 (11) | 2 (2) | 20 (7) |
| 2000–2004 | 24 (14) | 36 (28) | 60 (20) |
| 2005–2009 | 44 (26) | 81 (62) | 125 (42) |
| 2010–2014 | 83 (49) | 11 (8) | 94 (31) |
| Reproductive material stored, n (%)a | |||
| Oocytes | 60 (35) | N/a | |
| Ovarian tissue | 68 (40) | N/a | |
| Embryos | 62 (36) | 0 | |
| Sperm | N/a | 129 (98) | |
| Testicular tissue | N/a | 5 (4) | |
| Number of eggs mean (SD) | 11.6 (8.94) | N/a | |
| Number of embryos mean (SD) | 6.4 (5.12) | N/a | |
| Women | Men | All | |
|---|---|---|---|
| Age at cancer diagnosis mean (SD) | 30.3 (7.24) | 28.2 (9.21) | 29.4 (8.20) |
| Age at time of survey mean (SD) | 37.2 (7.05) | 37.2 (9.31) | 37.2 (8.10) |
| Relationship status at cancer diagnosis, n (%) | |||
| Single | 96 (56) | 85 (65) | 181 (60) |
| Married/co-habiting | 74 (44) | 45 (35) | 119 (40) |
| Relationship status at time of survey, n (%) | |||
| Single | 59 (35) | 50 (38) | 109 (36) |
| Married/co-habiting | 111 (65) | 80 (62) | 191 (64) |
| Year material stored, n (%) | |||
| 1995–1999 | 18 (11) | 2 (2) | 20 (7) |
| 2000–2004 | 24 (14) | 36 (28) | 60 (20) |
| 2005–2009 | 44 (26) | 81 (62) | 125 (42) |
| 2010–2014 | 83 (49) | 11 (8) | 94 (31) |
| Reproductive material stored, n (%)a | |||
| Oocytes | 60 (35) | N/a | |
| Ovarian tissue | 68 (40) | N/a | |
| Embryos | 62 (36) | 0 | |
| Sperm | N/a | 129 (98) | |
| Testicular tissue | N/a | 5 (4) | |
| Number of eggs mean (SD) | 11.6 (8.94) | N/a | |
| Number of embryos mean (SD) | 6.4 (5.12) | N/a | |
aSome respondents stored more than one type of reproductive material.
Respondent characteristics (n = 301).
| Women | Men | All | |
|---|---|---|---|
| Age at cancer diagnosis mean (SD) | 30.3 (7.24) | 28.2 (9.21) | 29.4 (8.20) |
| Age at time of survey mean (SD) | 37.2 (7.05) | 37.2 (9.31) | 37.2 (8.10) |
| Relationship status at cancer diagnosis, n (%) | |||
| Single | 96 (56) | 85 (65) | 181 (60) |
| Married/co-habiting | 74 (44) | 45 (35) | 119 (40) |
| Relationship status at time of survey, n (%) | |||
| Single | 59 (35) | 50 (38) | 109 (36) |
| Married/co-habiting | 111 (65) | 80 (62) | 191 (64) |
| Year material stored, n (%) | |||
| 1995–1999 | 18 (11) | 2 (2) | 20 (7) |
| 2000–2004 | 24 (14) | 36 (28) | 60 (20) |
| 2005–2009 | 44 (26) | 81 (62) | 125 (42) |
| 2010–2014 | 83 (49) | 11 (8) | 94 (31) |
| Reproductive material stored, n (%)a | |||
| Oocytes | 60 (35) | N/a | |
| Ovarian tissue | 68 (40) | N/a | |
| Embryos | 62 (36) | 0 | |
| Sperm | N/a | 129 (98) | |
| Testicular tissue | N/a | 5 (4) | |
| Number of eggs mean (SD) | 11.6 (8.94) | N/a | |
| Number of embryos mean (SD) | 6.4 (5.12) | N/a | |
| Women | Men | All | |
|---|---|---|---|
| Age at cancer diagnosis mean (SD) | 30.3 (7.24) | 28.2 (9.21) | 29.4 (8.20) |
| Age at time of survey mean (SD) | 37.2 (7.05) | 37.2 (9.31) | 37.2 (8.10) |
| Relationship status at cancer diagnosis, n (%) | |||
| Single | 96 (56) | 85 (65) | 181 (60) |
| Married/co-habiting | 74 (44) | 45 (35) | 119 (40) |
| Relationship status at time of survey, n (%) | |||
| Single | 59 (35) | 50 (38) | 109 (36) |
| Married/co-habiting | 111 (65) | 80 (62) | 191 (64) |
| Year material stored, n (%) | |||
| 1995–1999 | 18 (11) | 2 (2) | 20 (7) |
| 2000–2004 | 24 (14) | 36 (28) | 60 (20) |
| 2005–2009 | 44 (26) | 81 (62) | 125 (42) |
| 2010–2014 | 83 (49) | 11 (8) | 94 (31) |
| Reproductive material stored, n (%)a | |||
| Oocytes | 60 (35) | N/a | |
| Ovarian tissue | 68 (40) | N/a | |
| Embryos | 62 (36) | 0 | |
| Sperm | N/a | 129 (98) | |
| Testicular tissue | N/a | 5 (4) | |
| Number of eggs mean (SD) | 11.6 (8.94) | N/a | |
| Number of embryos mean (SD) | 6.4 (5.12) | N/a | |
aSome respondents stored more than one type of reproductive material.
Respondents’ reproductive experiences
Respondents’ reproductive experiences are shown in Table II. Half of the respondents had never tried to achieve a pregnancy. They were significantly younger than those who had tried to achieve a pregnancy (34.7 years versus 39.5 years, P < 0.001). Of those who had tried, some reported trying before the cancer diagnosis, some after, and others both before and after the diagnosis. One in ten respondents was a parent before the cancer was diagnosed and around one-third had had a child since diagnosis or was pregnant (or a partner in pregnancy) at the time of the survey.
Respondents’ reproductive experiences (n = 301).
| All | Women | Men | P-value | |
|---|---|---|---|---|
| Ever tried to get pregnant (with partner), n (%) | ||||
| No | 149 (50) | 76 (44) | 73 (57) | 0.013 |
| Yes, before cancer diagnosis | 30 (10) | 23 (14) | 7 (6) | |
| Yes, after cancer diagnosis | 90 (30) | 58 (34) | 32 (25) | |
| Yes, both before and after cancer diagnosis | 29 (10) | 13 (8) | 16 (12) | |
| Had child/children before cancer diagnosis, n (%) | 34 (11) | 18 (11) | 16 (12) | NS |
| Had child/children since cancer diagnosis or currently pregnant, n (%) | ||||
| No | 202 (67) | 114 (67) | 88 (67) | NS |
| Yes, as a result of natural conception | 58 (19)a | 42 (25) | 16 (12)a | 0.028 |
| Yes, as a result of ART with fresh material | 10 (3) | 10 (6) | 0 | <0.001 |
| Yes, as a result of ART with stored material | 32 (11)a | 4 (2) | 28 (21)a | <0.001 |
| Ideal number of children, n (%) | ||||
| 0 | 9 (3) | 5 (3) | 4 (3) | 0.114 |
| 1 | 41 (15) | 29 (18) | 12 (10) | |
| ≥2 | 233 (82) | 124 (79) | 109 (87) | |
| Expected number of children considering circumstances, n (%) | ||||
| 0 | 40 (13) | 25 (15) | 15 (12) | 0.021 |
| 1 | 48 (16) | 36 (21) | 12 (9) | |
| ≥2 | 146 (49) | 75 (44) | 71 (54) | |
| Don’t know | 67 (22) | 34 (20) | 33 (25) | |
| Want a(nother) child, n (%) | ||||
| No | 79 (27) | 46 (28) | 33 (26) | 0.011 |
| Yes | 200 (68) | 107 (64) | 93 (73) | |
| Yes, but unable to | 15 (5) | 14 (8) | 1 (1) | |
| All | Women | Men | P-value | |
|---|---|---|---|---|
| Ever tried to get pregnant (with partner), n (%) | ||||
| No | 149 (50) | 76 (44) | 73 (57) | 0.013 |
| Yes, before cancer diagnosis | 30 (10) | 23 (14) | 7 (6) | |
| Yes, after cancer diagnosis | 90 (30) | 58 (34) | 32 (25) | |
| Yes, both before and after cancer diagnosis | 29 (10) | 13 (8) | 16 (12) | |
| Had child/children before cancer diagnosis, n (%) | 34 (11) | 18 (11) | 16 (12) | NS |
| Had child/children since cancer diagnosis or currently pregnant, n (%) | ||||
| No | 202 (67) | 114 (67) | 88 (67) | NS |
| Yes, as a result of natural conception | 58 (19)a | 42 (25) | 16 (12)a | 0.028 |
| Yes, as a result of ART with fresh material | 10 (3) | 10 (6) | 0 | <0.001 |
| Yes, as a result of ART with stored material | 32 (11)a | 4 (2) | 28 (21)a | <0.001 |
| Ideal number of children, n (%) | ||||
| 0 | 9 (3) | 5 (3) | 4 (3) | 0.114 |
| 1 | 41 (15) | 29 (18) | 12 (10) | |
| ≥2 | 233 (82) | 124 (79) | 109 (87) | |
| Expected number of children considering circumstances, n (%) | ||||
| 0 | 40 (13) | 25 (15) | 15 (12) | 0.021 |
| 1 | 48 (16) | 36 (21) | 12 (9) | |
| ≥2 | 146 (49) | 75 (44) | 71 (54) | |
| Don’t know | 67 (22) | 34 (20) | 33 (25) | |
| Want a(nother) child, n (%) | ||||
| No | 79 (27) | 46 (28) | 33 (26) | 0.011 |
| Yes | 200 (68) | 107 (64) | 93 (73) | |
| Yes, but unable to | 15 (5) | 14 (8) | 1 (1) | |
aOne man had a naturally conceived and an ART-conceived child.
Respondents’ reproductive experiences (n = 301).
| All | Women | Men | P-value | |
|---|---|---|---|---|
| Ever tried to get pregnant (with partner), n (%) | ||||
| No | 149 (50) | 76 (44) | 73 (57) | 0.013 |
| Yes, before cancer diagnosis | 30 (10) | 23 (14) | 7 (6) | |
| Yes, after cancer diagnosis | 90 (30) | 58 (34) | 32 (25) | |
| Yes, both before and after cancer diagnosis | 29 (10) | 13 (8) | 16 (12) | |
| Had child/children before cancer diagnosis, n (%) | 34 (11) | 18 (11) | 16 (12) | NS |
| Had child/children since cancer diagnosis or currently pregnant, n (%) | ||||
| No | 202 (67) | 114 (67) | 88 (67) | NS |
| Yes, as a result of natural conception | 58 (19)a | 42 (25) | 16 (12)a | 0.028 |
| Yes, as a result of ART with fresh material | 10 (3) | 10 (6) | 0 | <0.001 |
| Yes, as a result of ART with stored material | 32 (11)a | 4 (2) | 28 (21)a | <0.001 |
| Ideal number of children, n (%) | ||||
| 0 | 9 (3) | 5 (3) | 4 (3) | 0.114 |
| 1 | 41 (15) | 29 (18) | 12 (10) | |
| ≥2 | 233 (82) | 124 (79) | 109 (87) | |
| Expected number of children considering circumstances, n (%) | ||||
| 0 | 40 (13) | 25 (15) | 15 (12) | 0.021 |
| 1 | 48 (16) | 36 (21) | 12 (9) | |
| ≥2 | 146 (49) | 75 (44) | 71 (54) | |
| Don’t know | 67 (22) | 34 (20) | 33 (25) | |
| Want a(nother) child, n (%) | ||||
| No | 79 (27) | 46 (28) | 33 (26) | 0.011 |
| Yes | 200 (68) | 107 (64) | 93 (73) | |
| Yes, but unable to | 15 (5) | 14 (8) | 1 (1) | |
| All | Women | Men | P-value | |
|---|---|---|---|---|
| Ever tried to get pregnant (with partner), n (%) | ||||
| No | 149 (50) | 76 (44) | 73 (57) | 0.013 |
| Yes, before cancer diagnosis | 30 (10) | 23 (14) | 7 (6) | |
| Yes, after cancer diagnosis | 90 (30) | 58 (34) | 32 (25) | |
| Yes, both before and after cancer diagnosis | 29 (10) | 13 (8) | 16 (12) | |
| Had child/children before cancer diagnosis, n (%) | 34 (11) | 18 (11) | 16 (12) | NS |
| Had child/children since cancer diagnosis or currently pregnant, n (%) | ||||
| No | 202 (67) | 114 (67) | 88 (67) | NS |
| Yes, as a result of natural conception | 58 (19)a | 42 (25) | 16 (12)a | 0.028 |
| Yes, as a result of ART with fresh material | 10 (3) | 10 (6) | 0 | <0.001 |
| Yes, as a result of ART with stored material | 32 (11)a | 4 (2) | 28 (21)a | <0.001 |
| Ideal number of children, n (%) | ||||
| 0 | 9 (3) | 5 (3) | 4 (3) | 0.114 |
| 1 | 41 (15) | 29 (18) | 12 (10) | |
| ≥2 | 233 (82) | 124 (79) | 109 (87) | |
| Expected number of children considering circumstances, n (%) | ||||
| 0 | 40 (13) | 25 (15) | 15 (12) | 0.021 |
| 1 | 48 (16) | 36 (21) | 12 (9) | |
| ≥2 | 146 (49) | 75 (44) | 71 (54) | |
| Don’t know | 67 (22) | 34 (20) | 33 (25) | |
| Want a(nother) child, n (%) | ||||
| No | 79 (27) | 46 (28) | 33 (26) | 0.011 |
| Yes | 200 (68) | 107 (64) | 93 (73) | |
| Yes, but unable to | 15 (5) | 14 (8) | 1 (1) | |
aOne man had a naturally conceived and an ART-conceived child.
Reproductive outcomes for those who had tried to conceive since being diagnosed with cancer are shown in Fig. 1. Of the 119 women and men who had tried to conceive since completing cancer treatment 84% (79% of women and 90% of men) had given birth or were currently pregnant (or a partner in pregnancy). Most of the pregnancies since the diagnosis of cancer occurred after natural conception (58/100, 58%). Women were more likely than men to have achieved pregnancy from natural conception (75% versus 36%, P = <0.001) but less likely to have conceived as a result of using their stored material (7% versus 64%, P < 0.001). Eighteen per cent of women had conceived with ART using fresh oocytes or embryos.
Reproductive outcomes of respondents who had tried to conceive since cancer diagnosis. *One man had fathered both a naturally and an ART-conceived child.
Respondents’ reproductive aspiration
Most women and men ideally wanted at least two children (78% and 87%, respectively) but when asked how many children they expected to have, considering their circumstances, fewer (44% and 54%, respectively) expected to achieve the ideal. Fifteen per cent of women and 12% of men expected to remain childless (Table II).
When asked if they wished to have a child or another child now or in the future, almost three quarters stated that they did. Respondents who wanted children in the future were significantly younger than those who did not (34.9 years versus 41.8 years, P < 0.001). Of those who wished to have children, some knew that this was not possible (Table II).
Use of stored material
In all 57 (19%) respondents had used their stored reproductive material in ART procedures (including IUI): 22 women and 35 men. As a proportion of those who had tried to conceive this represented 31% (22/71) of women and 73% (35/48) of men. Women were significantly less likely than men to have used their stored material (13% versus 27%, P = 0.002 of all and 31% versus 73%, P = 0.009 of those who had tried to conceive). Of those who had used it, women were less likely than men to have had a baby or to be currently pregnant (or a partner in pregnancy) as a result (18% versus 80%, P < 0.001). The outcomes of using stored material are shown in Table III. Of the four women who reported that they had had a baby or were currently pregnant from the stored material two had given birth, one was pregnant after the transfer of two embryos (one stored before cancer treatment and one fresh embryo created after treatment), and one woman reported that a surrogate was currently pregnant after the transfer of an embryo stored before cancer treatment.
Outcomes of using stored material in ART (including IUI) (n = 57).
| Outcomea | All | Women (n = 22) | Men (n = 35) | P-value |
|---|---|---|---|---|
| Year material stored | ||||
| 1995–2009 | 43 (75) | 9 (41) | 30 (86) | <0.01 |
| 2010–2013 | 14 (25) | 13 (59) | 5 (14) | |
| Thawing was unsuccessful, n (%) | 7 (12) | 6 (27) | 1 (3) | 0.01 |
| Thawing successful but no embryos formed, n (%) | 8 (14) | 5 (23) | 3 (9) | NS |
| Embryos formed but no pregnancy, n (%) | 22 (39) | 10 (45) | 12 (34) | NS |
| Experienced pregnancy loss, n (%) | 9 (16) | 3 (14) | 6 (17) | NS |
| Had a baby or pregnant (partner pregnant), n (%) | 32 (56) | 4 (18) | 28 (80) | <0.001 |
| Outcomea | All | Women (n = 22) | Men (n = 35) | P-value |
|---|---|---|---|---|
| Year material stored | ||||
| 1995–2009 | 43 (75) | 9 (41) | 30 (86) | <0.01 |
| 2010–2013 | 14 (25) | 13 (59) | 5 (14) | |
| Thawing was unsuccessful, n (%) | 7 (12) | 6 (27) | 1 (3) | 0.01 |
| Thawing successful but no embryos formed, n (%) | 8 (14) | 5 (23) | 3 (9) | NS |
| Embryos formed but no pregnancy, n (%) | 22 (39) | 10 (45) | 12 (34) | NS |
| Experienced pregnancy loss, n (%) | 9 (16) | 3 (14) | 6 (17) | NS |
| Had a baby or pregnant (partner pregnant), n (%) | 32 (56) | 4 (18) | 28 (80) | <0.001 |
aMultiple outcomes from repeated thawing procedures reported.
Outcomes of using stored material in ART (including IUI) (n = 57).
| Outcomea | All | Women (n = 22) | Men (n = 35) | P-value |
|---|---|---|---|---|
| Year material stored | ||||
| 1995–2009 | 43 (75) | 9 (41) | 30 (86) | <0.01 |
| 2010–2013 | 14 (25) | 13 (59) | 5 (14) | |
| Thawing was unsuccessful, n (%) | 7 (12) | 6 (27) | 1 (3) | 0.01 |
| Thawing successful but no embryos formed, n (%) | 8 (14) | 5 (23) | 3 (9) | NS |
| Embryos formed but no pregnancy, n (%) | 22 (39) | 10 (45) | 12 (34) | NS |
| Experienced pregnancy loss, n (%) | 9 (16) | 3 (14) | 6 (17) | NS |
| Had a baby or pregnant (partner pregnant), n (%) | 32 (56) | 4 (18) | 28 (80) | <0.001 |
| Outcomea | All | Women (n = 22) | Men (n = 35) | P-value |
|---|---|---|---|---|
| Year material stored | ||||
| 1995–2009 | 43 (75) | 9 (41) | 30 (86) | <0.01 |
| 2010–2013 | 14 (25) | 13 (59) | 5 (14) | |
| Thawing was unsuccessful, n (%) | 7 (12) | 6 (27) | 1 (3) | 0.01 |
| Thawing successful but no embryos formed, n (%) | 8 (14) | 5 (23) | 3 (9) | NS |
| Embryos formed but no pregnancy, n (%) | 22 (39) | 10 (45) | 12 (34) | NS |
| Experienced pregnancy loss, n (%) | 9 (16) | 3 (14) | 6 (17) | NS |
| Had a baby or pregnant (partner pregnant), n (%) | 32 (56) | 4 (18) | 28 (80) | <0.001 |
aMultiple outcomes from repeated thawing procedures reported.
Most respondents (81%) had not used their stored material. Reasons for not using the stored material were listed and respondents asked to endorse all that applied to them.
The five most commonly stated reasons for not using the stored material are shown in Table IV. Men were more likely than women to endorse not yet being ready to try for a baby and preferring to attempt natural conception first. Women were more likely than men to report that they (their partner) had conceived naturally. Eleven respondents had discarded their reproductive material (6 women and 5 men).
Reasons for not using stored reproductive material (n = 244).
| Reasona | All | Women | Men | P-value |
|---|---|---|---|---|
| I’m not yet ready to try for a baby, n (%) | 102 (42) | 48 (32) | 54 (56) | <0.001 |
| I plan to use it in the future, n (%) | 72 (30) | 41 (28) | 31 (32) | NS |
| I/my partner conceived naturally, n (%) | 52 (21) | 38 (26) | 14 (15) | 0.04 |
| Prefer to see whether we can conceive naturally, n (%) | 48 (20) | 21 (14) | 27 (28) | 0.007 |
| I am not in good enough health, n (%) | 18 (7) | 15 (10) | 3 (3) | 0.04 |
| Reasona | All | Women | Men | P-value |
|---|---|---|---|---|
| I’m not yet ready to try for a baby, n (%) | 102 (42) | 48 (32) | 54 (56) | <0.001 |
| I plan to use it in the future, n (%) | 72 (30) | 41 (28) | 31 (32) | NS |
| I/my partner conceived naturally, n (%) | 52 (21) | 38 (26) | 14 (15) | 0.04 |
| Prefer to see whether we can conceive naturally, n (%) | 48 (20) | 21 (14) | 27 (28) | 0.007 |
| I am not in good enough health, n (%) | 18 (7) | 15 (10) | 3 (3) | 0.04 |
aMultiple reasons could be stated.
Reasons for not using stored reproductive material (n = 244).
| Reasona | All | Women | Men | P-value |
|---|---|---|---|---|
| I’m not yet ready to try for a baby, n (%) | 102 (42) | 48 (32) | 54 (56) | <0.001 |
| I plan to use it in the future, n (%) | 72 (30) | 41 (28) | 31 (32) | NS |
| I/my partner conceived naturally, n (%) | 52 (21) | 38 (26) | 14 (15) | 0.04 |
| Prefer to see whether we can conceive naturally, n (%) | 48 (20) | 21 (14) | 27 (28) | 0.007 |
| I am not in good enough health, n (%) | 18 (7) | 15 (10) | 3 (3) | 0.04 |
| Reasona | All | Women | Men | P-value |
|---|---|---|---|---|
| I’m not yet ready to try for a baby, n (%) | 102 (42) | 48 (32) | 54 (56) | <0.001 |
| I plan to use it in the future, n (%) | 72 (30) | 41 (28) | 31 (32) | NS |
| I/my partner conceived naturally, n (%) | 52 (21) | 38 (26) | 14 (15) | 0.04 |
| Prefer to see whether we can conceive naturally, n (%) | 48 (20) | 21 (14) | 27 (28) | 0.007 |
| I am not in good enough health, n (%) | 18 (7) | 15 (10) | 3 (3) | 0.04 |
aMultiple reasons could be stated.
Effects of cancer treatment on fertility potential
Respondents were asked if they had consulted a doctor about their fertility potential since storing reproductive material. Of the 152 women who responded to this question 85 (56%) had done so. Of these 28 (33%) had found out that they were still potentially fertile and 23 (27%) that they were not; 34 (40%) were still undergoing investigations or fertility treatment. Among the men 49/126 (39%) had seen a doctor about their fertility and 24 (49%) of them had learned that they were still potentially fertile and 16 (33%) that they were not; 9 (18%) were arranging to have their fertility potential tested.
Women were asked if their menstrual pattern had changed since undergoing cancer treatment. Of the 167 who provided a response to the question, 36 (22%) stated that they did not stop menstruating during chemotherapy, 71 (42%) that menstruation stopped but resumed after completing chemotherapy, and 47 (28%) that menstruation ceased and did not resume after chemotherapy. Thirteen (8%) women responded that they had had a hysterectomy or were still on hormone therapy as part of their cancer treatment regime and could not evaluate the effect of chemotherapy on menstruation.
Discussion
This is one of the largest follow-up studies to date, and the first from Australia, of people who freeze reproductive material before undergoing cancer treatment. The findings add to the limited evidence about the reproductive outcomes in this group of people whose numbers continue to grow and can be used to inform the advice given to those contemplating fertility preservation in the context of cancer.
Strengths of this study include that complete cohorts of women and men who had stored reproductive material before cancer treatment at two private hospitals and one public hospital were invited to participate; it had a comparatively large number of respondents with diverse characteristics; and it elicited comprehensive information about reproductive hopes, expectations and outcomes among people who store reproductive material before cancer treatment. Nevertheless, we acknowledge the limitations of the study. First, there is no way of comparing the sample with the populations they were drawn from as data on reproductive outcomes of people who store reproductive material before cancer treatment are not collected routinely. This might have led to over- or underestimates of the reproductive experiences and outcomes reported in this paper. Second, the relatively low response rate, particularly among men, means that participation bias may have influenced the findings. It is not possible to know whether people with better or worse reproductive experiences were more or less likely to participate: we cannot therefore, speculate how the results may have differed if a higher participation rate had been achieved. Potential contributors to the low participation rate are that approval from the Human Research Ethics Committees was conditional on (a) anonymous participation, (b) that potential respondents were not contacted directly by the researchers and (c) that only one reminder to respond was sent. Third, because the type of cancer respondents had been diagnosed with was self-reported and we did not ask questions about the types of cancer treatments respondents had undergone, it is not possible to link reproductive outcomes to type of cancer or cancer treatment. Lastly, as we did not ask whether women were using hormonal contraception, it is possible that some of the women who stated that they still had menstrual cycles were referring to withdrawal bleeding.
While half of the respondents had not yet tried to conceive with a partner, overall three quarters of respondents were hoping to have a child in the future. However, potentially unfulfilled parenthood aspirations were evident: most expected to have fewer children than they would have ideally liked to have and many expected to remain childless. Loss of fertility after cancer treatment can lead to profound and long-lasting sadness and grief (Nieman et al., 2006; Kirkman et al., 2014). A follow-up study of 484 cancer survivors 3–7 years after treatment found that about a third of those who wished to have children were experiencing fertility difficulties and that an unfulfilled wish for a child was associated with worse mental health (Armuand et al., 2014). In the context of cancer, grief about infertility may be disenfranchized (Doka, 1999) as it may be perceived as insignificant compared to having overcome a threat to survival. Whether people store gametes or not before cancer treatment, appropriate counselling is important and should engage with the possibility of future involuntary childlessness, acknowledging the consequent potential for distress and disruption to life plans.
One-third of women and of men had had a child since completing cancer treatment or were pregnant (or a partner in pregnancy). Among the women this was mostly a result of natural conception; only 7% of conceptions resulted from stored reproductive material. However, almost half of the women had stored their reproductive material in the last 5 years and a high proportion of women who had not used their stored material still expected to do so, making it likely that more material will be used from which pregnancies might result in the future. In their follow-up of 68 women who had stored oocytes before cancer treatment Dahhan et al. (2014) found that none of the 16 who had been trying to conceive had used their stored oocytes. Most women in that study reported intending only to use their stored oocytes as a last resort.
Men were more likely than women to have become parents after using stored reproductive material but less likely to have achieved a natural pregnancy. Usage and achieved fatherhood rates in this study (27% and 80%, respectively) were much higher than the average reported in a review of 30 studies (8% and 49%, respectively) (Ferrari et al., 2016). However, there were large differences between the studies included in the review in usage rates (2–60%) and achieved fatherhood rates (0–82%). This may in part be explained by between-study differences in duration of follow-up time (between 4 years and 36 years). The study by Greaves et al. (2014) had a similar usage rate and the study by Sonnenburg et al. (2015) a similar rate of achieved fatherhood as in the observed in the current study.
The results of our survey indicate that a substantial proportion of women and men remain fertile after cancer treatment. At least one-third of the women who had seen a fertility specialist reported being told that they were still fertile and almost two-thirds had continued menstruating after completing cancer treatment. However, even if menstruation resumes after chemotherapy, women need to know that they are still at risk of developing premature menopause due to the damage of cancer treatment to their ovarian reserve (Poggio et al., 2016).
As the response rate in this study was relatively low, cancer diagnosis was self-reported and information about types of cancer treatment was not collected study findings may be indicative rather than generalizable to all people who freeze reproductive material before cancer treatment. National and international registries of large numbers of patients with diverse cancers and treatments offer the best prospect of generating evidence about fertility after cancer treatment, the potential benefits of fertility preservation and reproductive outcomes of cancer survivors. One such registry is The Australasian Oncofertility Registry, a web-based database collecting data from oncology and fertility centres in Australia and New Zealand (www.futurefertility.com.au). The cumulative data in this registry will allow clinicians to offer advice to patients about the potential benefits of fertility preservation options, taking account of their individual circumstances (Anazodo et al., 2016). Patients will then be better placed to make informed decisions about storing reproductive material before undergoing cancer treatment.
Conclusion
In this survey, the number of people who had returned to use their stored material was relatively low, especially among women. However, since many had frozen their reproductive material in recent years, the rate of usage is likely to increase. The high rate of successful pregnancies resulting from the use of stored sperm contrasts with the much lower rate from stored female reproductive material. While men can be reassured that frozen sperm retains its viability, women need to be aware that fertility preservation may not be an insurance against infertility but rather that it might add to the chance of achieving parenthood in the future. Women should also be informed that, although natural conception may be possible, they are at risk of premature menopause as a consequence of the cancer treatment.
Supplementary data
Supplementary data are available at Human Reproduction online.
Acknowledgements
We are grateful to the clinical staff at the three clinics who used their patient databases to identify potential respondents. We also thank Hau Nguyen and Carmin Smith for their assistance with data management and analysis.
Authors’ roles
All authors contributed to the conceptualization and design of the study. K.H., F.A. and G.C. managed data collection. K.H., M.K. and J.F. analysed and interpreted the data. KH wrote the first draft with contributions from all other authors. All authors approved the final draft.
Funding
This study was funded by a grant from the National Health and Medical Research Council (NHMRC APP1042347).
Conflict of interest
None declared.
