Preimplantation genetic diagnosis: patients’ experiences and attitudes

S.A. Lavery1,3, R. Aurell2, C. Turner1, C. Castello2, A. Veiga2, P.N. Barri2 and R.M. Winston1

1 Division of Paediatrics, Obstetrics and Gynaecology, Imperial College, Hammersmith Hospital and Du Cane Rd, London W12 0HS, UK and 2 Institut Universitari Dexeus, Department of Reproductive Medicine, Pg.Bonanova 67, 08017 Barcelona, Spain


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
BACKGROUND: This study aims to report the experiences and attitudes of patients who have undergone preimplantation genetic diagnosis (PGD). The extent to which this technique is acceptable to the individuals for whom it is intended is relatively unexplored, and remains a crucial issue that may ultimately determine the value of PGD as an alternative to prenatal diagnosis in high-risk couples. METHODS: An information sheet and questionnaire was distributed to 67 couples who had been treated at the Hammersmith Hospital, London and the Dexeus Institute, Barcelona. RESULTS: One-third of patients had an affected child, over half had previous experience of conventional prenatal diagnosis and over one-third had had terminations of pregnancy because of a genetic risk. Patients perceive the main advantage of PGD to be that only unaffected embryos are transferred to the uterus and thus therapeutic termination of pregnancy can be avoided; the main disadvantage is the low success rate. A total of 41% of patients found the treatment cycle extremely stressful, and, of the 20 patients who had experienced both prenatal diagnosis and PGD, 40% of patients found PGD less stressful, although 35% experienced more stress. Of those couples who contemplated a further pregnancy 76% would choose PGD, 16% would opt for prenatal diagnosis, and 8% no tests at all. CONCLUSIONS: The experience of prenatal diagnosis and termination of pregnancy can be an unwelcome memory and this leads to a demand for an alternative approach. Our data suggest that PGD is acceptable to patients and is a valuable alternative to prenatal diagnosis.

Key words: attitudes/experience/patient/preimplantation/stress


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Prenatal diagnosis of inherited disease conventionally involves sampling cells of fetal origin by amniocentesis in the second trimester of pregnancy, or chorionic villus sampling rather earlier. Detection of the specific genetic defect in that family can then usually be made by biochemical, cytogenetic or DNA analysis. Couples with a chance of having affected children face the risks associated with these diagnostic procedures and the difficult decision of whether to continue with an affected pregnancy. Some couples repeatedly terminate pregnancies in attempts to have a normal child (Soussis et al., 1996Go). As an alternative to conventional prenatal diagnosis, preimplantation genetic diagnosis (PGD) has an advantage. In selecting embryos identified as unaffected for transfer to the uterus, couples know from the beginning of the pregnancy that any baby born should not suffer from the genetic condition carried by the family.

The diagnosis of genetic disease in human preimplantation embryos was pioneered in the late 1980s (Handyside et al., 1989Go). Before then, carriers of genetic disorders had these options: remain childless, adopt, accept gamete donation, terminate a pregnancy or play ‘reproductive roulette’ with spontaneous conception (Fletcher, 1988Go). PGD improves the choices available to couples at risk of having children with genetic abnormalities. It also may provide reassurance and reduce anxiety associated with reproduction.

The extent to which this technique is acceptable to the individuals for whom it is intended is relatively unexplored. The general public has been consulted (Genuis et al., 1993Go; Macer, 1994Go; Human Genetics Commission, 2001Go), and the views of infertile people have been sought (Alder et al., 1986Go; Lyall et al., 1995Go). An international survey of the legal status of PGD has been conducted in thirteen countries (Viville and Pergament, 1998Go). Another study (Pergament, 1991Go) examined potential patients’ perspective of PGD. In a sample of 58 women who had previously experienced an affected pregnancy, 55% expressed a possible preference for PGD in the future rather than prenatal diagnosis. Miedzybrodzka et al. studied 474 women and found that most favoured prenatal diagnosis rather than PGD (43 versus 38%), with the exception, perhaps predictably, of those women who needed IVF because of infertility (Miedzybrodzka et al., 1993Go). Palomba et al. studied Sardinian women carrying ß-thalassaemia (Palomba et al., 1994Go). All those who had previously terminated a pregnancy thought of PGD as an acceptable alternative whilst only 30% those who had not had a pregnancy terminated thought it worth consideration. A woman’s obstetric experience may be highly relevant in her reproductive choice if at high risk of an affected pregnancy.

Snowdon and Green analysed attitudes to PGD, prenatal diagnosis, adoption and gamete donation in 245 carriers of recessive disorders. Attitudes towards PGD were positive but attitudes towards adoption and gamete donation were not. Men and women tended to differ though, and despite female support for PGD, prenatal diagnosis remained the most useful reproductive option (Snowdon and Green, 1997Go). Chamayou et al. confirmed that Sicilian patients carrying thalassaemia favoured PGD and emphasized the importance of previous experience of therapeutic abortion in determining attitudes (Chamayou et al., 1998Go).

As far as we are aware, this study represents the first assessment of couples who have actually undergone PGD. It documents their background experience of the genetic condition, and details the perceived advantages and disadvantages of the technique. We also reviewed the motivation of couples choosing PGD and the nature and timing of stress experienced during the treatment cycle. Perhaps most importantly, this survey compares and contrasts the experiences of prenatal diagnosis with PGD by couples who have been exposed to both forms of treatment.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
These data are based on analysis of two groups of couples who had undergone treatment involving PGD, the first at the Hammersmith Hospital, London between 1990 and 1998 and the second at the Dexeus Institute, Barcelona, between 1995 and 1998. A postal survey was mailed to 67 couples. The questionnaire included a covering letter explaining the purpose of the study, with contact telephone numbers for general inquiries. The questionnaire was designed in English and subsequently translated into Spanish. A telephone follow-up was employed following initial returns of the questionnaire.

The first part of the questionnaire was designed to gather background information concerning the couples became aware of their genetic condition and their experiences of having affected children, prenatal diagnosis and termination of affected pregnancies. The second part of the questionnaire elicited the couples’ experiences during the PGD treatment. We recorded the number of cycles they had, whether they felt stressed and when this stress occurred and what steps taken to alleviate it. We also attempted to assess the impact of the treatment cycle on the couple’s relationship with each other. The third part of the survey examined the couples’ attitudes to PGD: their perception of the advantages and disadvantages; their motivation for undertaking the treatment. The fourth and final section of the questionnaire compared the couples’ experiences of conventional prenatal diagnosis with PGD.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
A total of 67 questionnaires were sent out and 36 were returned (53%), all of which were valid. These 36 couples had undergone 79 PGD cycles. Ages of the women at the time of the treatment cycle were 25–41 years (median 33 years). The average number of treatment cycles that each couple had was 2, (range 1–8). A total of 81% of respondents claimed to have a religion, the largest groups were protestant (48%) and catholic (35%). A total of 25% of couples were carriers for cystic fibrosis, 56% were carriers of X-linked disorders and 17% of couples had chromosomal disorders.

The couples’ previous experience is recorded in Table IGo. One-third had an affected child, over half had previous experience of conventional prenatal diagnosis (either amniocentesis or chorionic villus sampling) and over one-third had had terminations of pregnancy because of a genetic risk. The overall pregnancy rate after PGD was 22% per cycle started.


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Table I. Patients’ experience of their genetic status
 
Stress or anxiety scores when performed up to 10 years after the event are unreliable, so couples were simply asked whether they recalled feeling stressed during the treatment. A total of 41% of patients found the treatment cycle extremely stressful, with two reporting it as the most stressful period of their lives. Overall, 35% experienced moderate stress, 23% found it mildly stressful, while two couples experienced no stress at all. We identified various stages when stress might be most likely to be experienced: the waiting time until treatment; ovarian stimulation, scans and blood tests; egg collection; biopsy result and embryo transfer; waiting for pregnancy result, and other. Most couples found the time waiting after embryo transfer for a pregnancy result and time waiting after the initial consultation before a treatment cycle most stressful. A total of 33% of couples felt that the treatment exerted a negative stress on their relationship, 33% felt it had a positive effect, and 33% experienced no effect on their relationship at all.

Table IIGo records couples’ perceptions of the advantages and disadvantages of PGD. The main advantage was the avoidance of termination of pregnancy. A decreased risk of miscarriage was recorded as very important in 33% of couples, probably representing those couples undergoing PGD for structural chromosomal abnormalities such as translocations. Couples were questioned as to their perceived chance of conceiving following PGD. A total of 41% felt that the chance of pregnancy was between 0 and 20%; 24% of couples believed their chance of conceiving was between 21 and 40%; and 35% of couples had expectations of pregnancy rates >41%. The final section of the questionnaire (Table IIIGo) compared the couples’ experiences of conventional prenatal diagnosis and PGD, and asked which treatment they might choose in the future.


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Table II. Attitudes to preimplantation genetic diagnosis
 

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Table III. Comparison of preimplantation genetic diagnosis (PGD) and conventional prenatal diagnosis
 
Several other pieces of information were provided by this survey. Only 37% of those patients becoming pregnant after PGD decided to undergo confirmatory prenatal diagnosis. Most of those deciding to have prenatal diagnosis were patients being treated at the beginning of the programme. Interestingly, 94% of couples felt that one potential advantage of PGD was the possibility of having twins.


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
It is a decade since the first successful delivery of twins following PGD (Handyside et al., 1990Go). During that time the technique has been subject to assessment of its safety and efficacy (Geraedts et al., 2000Go). What has been lacking is an objective evaluation of its acceptability. PGD is expensive and labour intensive, requiring expertise in reproductive endocrinology, embryology and molecular genetics. Patient acceptability is one crucial issue that may ultimately determine the value of PGD as an alternative to prenatal diagnosis in high-risk couples.

The response rate in our study was 53%. This is a disappointing response given the commitment of both patients and carers in initiating and delivering this technology. A telephone follow-up of non-responders was used to improve the response rate. It does compare reasonably favourably with previous studies [47% (Pergament, 1991Go), 52% (Snowdon and Green, 1997Go)] though in these studies the questions surrounding the use of PGD were of mere academic interest in that these subjects did not commit themselves to a treatment. The rather poor response could possibly be explained by a 10-year time lapse between treatment and questionnaire in some cases. Snowdon and Green detected some differences between men and women in their perceptions of the advantages and disadvantages of PGD. Although all our questionnaires were addressed to the couple, 100% of responses were returned by the female partner, and no separate specific attempt was made to determine the views of the male partner.

Palomba predicted that previous obstetric experience would be crucial in the reproductive choices of women at high genetic risk. Our data confirm this: 31% had an affected child, 56% had prenatal diagnosis and 36% had undergone a therapeutic termination of pregnancy for the genetic condition (Table IGo). Snowdon and Green showed that most couples would opt for conventional prenatal diagnosis. Our data suggest that the experience of prenatal diagnosis and termination of pregnancy is an unwelcome memory and this leads to a demand for an alternative approach.

The main advantage of PGD perceived by patients is that only unaffected embryos are transferred to the uterus and thus therapeutic termination of pregnancy can be avoided (Table IIGo). Initial studies predicted this, and our work confirms that this is the major motivating factor for patients choosing PGD. PGD is also performed for chromosomal disorders such as translocations and a decreased risk of miscarriage is also seen as a major advantage of PGD. Our subjects felt that the low success rate was the main disadvantage. The take-home baby rate from PGD is at best 15–20% per cycle started. As the majority of couples undergoing cycles are fertile, it is unsurprising that this is a most significant factor. Interestingly, it has been estimated that a fertile couple has only a 20% chance of conceiving in each ovulatory cycle (Hull, 1990Go). Whilst few of our patients (~30%) were self-funded, cost is considered to be another significant disadvantage. Pergament calculated that if the cost of a PGD cycle exceeded that of a conventional cycle, then only one in seven high-risk patients would find PGD affordable in North America. In Europe the cost may be borne by the state but PGD cycles are often funded from already over-stretched fertility budgets and couples carrying genetic defects often have to compete for these resources (Lavery et al., 1999Go). The risk of misdiagnosis is a serious disadvantage and most of the major centres over the last 10 years have had this problem sporadically (Handyside et al., 1990Go; Sermon 1998Go).

Couples at risk of transmitting genetic disease to their children frequently experience stress, depression and anxiety (Marteau et al., 1997Go; Wellisch et al., 1999Go). The psychological impact of termination of pregnancy is stressful and traumatic (Donnai et al., 1981Go; Black 1989Go) and the grief experienced following termination for abnormality can be similar to that following neonatal death (Kenyon, 1988Go). PGD is an alternative that may be more acceptable but, of course, undergoing IVF itself is associated with stress and anxiety (Williams, 1989Go; Crowe, 1990Go). These couples are therefore uniquely vulnerable. A total of 41% of our patients found the PGD cycle extremely stressful. This had an adverse effect on the couples’ relationship in one third of cases, but brought another third closer together. Overall, 40% of couples who had experience of prenatal diagnosis and PGD found PGD less stressful. However, 35% of this group felt more stress when undergoing PGD (Table IIIGo). Perhaps most importantly, of those couples who contemplated a further pregnancy, 77% (20/26) felt that they would choose PGD, whilst 15% (4/26) would opt for prenatal diagnosis, and 8% no tests at all (Table IIIGo).

More than 90% of couples made use of, and were satisfied with, genetic counselling. However, <30% of couples made use of the specialist IVF counsellors before or during the treatment cycle, and 65% of couples expressed a wish to use this counselling service in any future cycle and it is possible this may alleviate some of their stress. In response to some of the open-ended questions such as ‘how would you advise other couples having PGD’, there were recurring themes of establishing good communication, obtaining accurate information and maintaining realistic expectations. Patients may overestimate the chance of successful treatment, so proper communication is clearly vital if false optimism is to be avoided.

PGD is not an easy solution for high-risk genetic couples (Atkinson and Handyside, 1994Go). This technique is still in its infancy and it should be remembered that both chorionic villus sampling and amniocentesis were performed for many years before they became clinically accepted. Our data suggest that PGD is acceptable to patients and is a valuable alternative to prenatal diagnosis.


    Notes
 
3 To whom correspondence should be addressed. E-mail: stuart.lavery{at}ic.ac.uk Back


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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
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Submitted on February 26, 2002; accepted on May 8, 2002.