Family situation
Rb risk for (future) offspring (%)a
Counselee is a carrier of a germline RB1 mutation
50
Counselee has had unilateral non-familial Rb, without a detectable germline RB1 mutation
0.5–1
Counselees are healthy parents of a child with a de novo RB1 mutation
2–3
Counselees are healthy parents of a child with unilateral non-familial Rb without a detectable germline RB1 mutation
<1
Couples with an increased risk have several reproductive options. They may decide to remain childless, or, if they already have an affected child, have no more children.
They may adopt a child or choose gamete donation. If a germline RB1 mutation is detected, couples can choose prenatal diagnosis (PND). If the child is a carrier of the mutation, they could opt for termination of the pregnancy, although some may find termination of a pregnancy of a potentially treatable disease debatable.
If one of the parents is a RB1 mutation carrier, preimplantation genetic diagnosis (PGD) may also be an option to avoid the birth of an affected child. PGD involves DNA testing of the parental RB1 mutation in two cells of a 3-day old embryo during in vitro fertilization. Only embryos without the mutation are transferred to the uterus. Alternatively, couples can decide to accept the risk and have biological children without using the above mentioned options. Genetic counseling may facilitate informed reproductive decision-making by couples at increased risk of a child with Rb. To accommodate the needs of these couples, it is important to obtain more insight into their reproductive behavior and into difficulties they may experience. In this chapter the current knowledge about reproductive decision-making of couples at increased risk of a child with retinoblastoma is discussed.
Reproductive Decision-Making Process
Little is known about the reproductive decision-making process of affected individuals with Rb or of healthy parents with a child with Rb. Several studies, however, have examined reproductive decision-making of couples at increased risk of having a child with another hereditary disease. One study in the Netherlands, for example, did a follow-up study of 164 couples who had visited a Clinical Genetics Department for a variety of disorders concerning childbearing (Frets et al. 1991) during the 1980s. Forty-three percent of the couples experienced the reproductive decision-making process as difficult, had doubts about the decision that was made, or were unable to make a decision. Factors associated with problems in the decision-making process in these couples were: no post-counseling relief, anticipation of a high risk of affected children prior to counseling, relatives’ disapproval of the decision, a decision against having children and the presence of an affected child (Frets et al. 1991). A more recent study by (Kelly 2009) showed that parents of children with a genetic condition or impairment may not pursue further childbearing or decline the use of prenatal diagnostics, in order to avoid making a difficult decision (Kelly 2009), i.e., parents chose not to choose. As was already shown in 1979, in the study by Lippman-Hand: parents tend to make a “non-decision” if they are not able to process the “facts” to provide a sense of coping (Lippman-Hand and Fraser 1979a).
Dommering et al. published a qualitative interview study of 14 couples of childbearing age at increased risk for a child with Rb, exploring the impact of prospective risk on reproductive decisions and the needs of couples with regard to reproductive counseling (Dommering et al. 2010). This study was followed by a cross-sectional questionnaire survey among 81 individuals with an increased risk of a child with Rb (Dommering et al. 2012). The results show that 44% of the 81 respondents from all four risk groups (see Table 9.1) had had doubts about their reproductive decisions as a result of Rb, while 38% had changed their minds about their decision whether or not to have any (or more) children. Some respondents changed their opinion and decided not to have another child, after having a child with Rb. This can be illustrated with quotes from the qualitative study (Dommering et al. 2010), like this couple with a child with a de novo RB1 mutation:
That second pregnancy was emotionally heavy. It was a hell in a way. […] I really wanted three children, but now I am hesitating. I mean, I have two healthy children [one with bilateral Rb], all is going well. I don’t want to tempt fate. I feel Rb should not rule your life, but basically it does.
Others changed their mind the other way, deciding to have children (or more children), for different reasons: e.g., some time having passed since treatment of their child, after testing negative for a germline RB1 mutation, after talking to other parents of affected children. This is illustrated by the following comment of another healthy couple with a child affected by hereditary Rb:
We always wanted to have two children. But after we had X [child with Rb] we never wanted to go through this process ever again. […] But after you get out of the hospital, you forget what you have been through. And your child is playing again and everything is all right and you start to think: Well, it doesn’t have to happen again…
These results clearly show that for many couples at increased risk of having a child with Rb, having children is not self-evident.
Reproductive Behavior
Again, few studies have addressed the actual reproductive behavior of couples at increased risk of a child with Rb. Based on research primarily aimed at investigating other aspects of living with Rb (Byrne et al. 1995; van Dijk et al. 2010; Cohen et al. 2001), it appears that for many individuals the risk of Rb influences childbearing. One study from the USA described the long-term effects of a genetic testing service for families with a child with unilateral, non-familial Rb (Cohen et al. 2001). It was found that RB1 testing of these children influenced parents’ decision to have more children in 20% (10/49) of the families. In the early 1980s, Byrne et al. interviewed 56 Rb survivors, diagnosed before 1962, to assess long-term consequences of Rb (Byrne et al. 1995). Fifteen of these Rb patients had a 50% risk for a child with Rb. One of their main findings was that fewer married Rb survivors than controls reported a pregnancy. Moreover, of the female survivors who married and became pregnant, 42% had only one pregnancy compared to 16% of female controls. The authors concluded that these differences reflected lifestyle or personal choices more than impaired fertility (Byrne et al. 1995). However, these patients were interviewed in the pre-molecular era, making it difficult to use this data in current-day practice. Van Dijk et al. interviewed Dutch Rb survivors in 2005/2006 and found that 68% of the 38 adult hereditary Rb survivors and 32% of the 54 non-hereditary Rb survivors indicated that Rb had an impact on their desire to have children (van Dijk et al. 2010). Overall, 12% of all 92 adult Rb survivors in their study decided not to have children due to the increased risk of having a child with Rb.
In the questionnaire study by Dommering et al. (2012) 43 of the 81 respondents were considering children after becoming aware of their increased recurrence risk (Dommering et al. 2012). Twenty-five (58%) of these 43 respondents reported that they had changed their reproductive behavior because of Rb; 20 (80%) decided against having any (or more) children, including 11 respondents with a recurrence risk of less than 3%. A healthy couple with a child with unilateral Rb, without a detectable RB1 mutation put it this way:
We would have considered another child. But now we decided against it. […] We didn’t want to go through this another time. The agony! They say it’s not hereditary, but still…
A couple with a 50% risk decided not to have any children at all:
I think Rb is a very serious disease and looking at it that way, you know, that decides I don’t want to try it. I know for sure I don’t want a child with Rb.
In many centers, prenatal diagnosis (PND) is available for couples at risk. In PND, DNA-testing of the familial RB1 mutation is performed during early pregnancy, with the option to terminate the pregnancy if the fetus is affected. Five couples out of the 43 respondents considering children from the study of Dommering et al. (2012) had used chorionic villi sampling to determine whether the fetus was affected, including three healthy couples with a child affected by hereditary Rb and a recurrence risk of 2–3% (Dommering et al. 2012). Like this healthy couple who became pregnant again shortly after their first child started intensive treatment for hereditary Rb and who chose to do PND.
We were barely thinking about the pregnancy, only in a way like: checking, checking, and checking. We were 180% busy with X [child with Rb] and I kept thinking: what if X’s treatment is not finished and we will have to go to the hospital with the new baby? We will get a problem who to give our attention to. So to get more certainty, we did the test.
Eighteen of the forty-three respondents who had considered having children after becoming aware of their increased risk, decided to have a (subsequent) child and did not choose any of the alternative reproductive options (Dommering et al. 2012). A woman affected by hereditary Rb, who did not feel like using PND or PGD said:
It feels for me like going to the market and buying yourself a baby. […] You don’t take a child, you get one and you get it like it is. Actually, that is how it’s meant to be. […] You know life after Rb is a good and complete life, it’s what you make of it.
Several studies have also documented pre-implantation genetic diagnosis (PGD) for Rb (Xu et al. 2004; Dommering et al. 2004; Rechitsky et al. 2002; Girardet et al. 2003). Since 1999, ten couples have been referred for PGD in the Netherlands and four couples in effect decided to go through with the procedure (Dommering et al. 2012).
Several studies about reproductive decisions of individuals at increased risk for children with other genetic diseases have also found that many decide against having more children to avoid having an affected child. For example, 41% of 230 parents of children with metabolic diseases (Read 2002) and 32% of 181 parents of children with cystic fibrosis had no further children (Henneman et al. 2001). Two studies on reproductive decisions of hemophilia carriers showed that carriers not choosing PND often decided not to have any (or more) children (Tedgard et al. 1999; Kadir et al. 2000).
In studies assessing attitudes towards PND and/or PGD for other hereditary cancers (Levy and Richard 2000; Kastrinos et al. 2007; Lammens et al. 2009; Douma et al. 2009), between 33 and 71% considered the use of these methods to avoid the birth of an affected child. The recurrence risk in these studies was 50%. In the study by Dommering et al. (2012) some of the couples who decided to have PND for Rb were healthy couples with a child with a de novo RB1 mutation, with a recurrence risk of 2–3% (Dommering et al. 2012). So in the case of Rb, even couples with a relatively small recurrence risk may decide to opt for PND.
Factors of Influence on Reproductive Decision-Making
Several factors, such as the perceived burden and familiarity with the disorder, can be of influence on reproductive decisions of couples at increased risk of a child with a genetic disorder (Frets et al. 1990; Henneman et al. 2002). With regard to Rb, type of treatment was associated with reproductive decisions, such as whether or not to have (further) children or use assisted reproductive technologies. Treatment with bilateral enucleation, chemotherapy and/or radiotherapy was more of influence on reproductive decisions than treatment with just unilateral enucleation and/or local therapy (Dommering et al. 2012):
You can’t explain to your child what’s happening. He is suffering but doesn’t know what’s happening at all. […] Due to the chemotherapy his skin was ruined and changing diapers became very painful. So with a second child you risk having to go through this again. No, we couldn’t face it.
A study of the quality of life of adult Rb survivors concluded that bullying in childhood was one of the predictors of a worse quality of life (van Dijk et al. 2007). For some Rb survivors the sequellae of treatment of Rb (impaired vision, cosmetic deformities due to treatment) have an impact on their social life and sometimes these negative experiences also influence reproductive decision-making. Like this person, who had been treated for bilateral Rb by external beam radiotherapy, which had lead to orbital deformity and who chose PND:
Yes, my childhood has been unpleasant. I was bullied for being different, until halfway through high school, day in and day out: they beat me up, they ruined my glasses, and they nicked my stuff. […] I don’t want this for my child, such a life.
Other aspects that were shown to be of influence on reproductive behavior were the perceived consequences of Rb (Dommering et al. 2012). This included factors such as the risk of passing Rb on to offspring, the risk of a child with impaired vision or blindness and fear or worries about developing second primary tumors later in life. A couple at 50% risk said:
We decided that we would terminate the pregnancy if the child turned out to be a carrier. […] They can’t predict the severity of the disease. We were afraid it [the child] would be blind at birth or that it would not survive cancer. I know someone who has lost a child to retinoblastoma. I absolutely would not want to live through that.Related posts:
The Concept of a Preniche for Localization of Future Metastases
Use of Mobile Phones and Brain Cancer Risk in Children?
Metastatic Oligodendroglioma: Diagnosis with Fine-Needle Aspiration Cytology
Lipoma: An Overview
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