Reasons for discontinuation from fertility treatment across different treatment stages. Data concerning reasons that cannot be considered discontinuation because they refer to external constraints to treatment uptake (e.g., doctor censuring, financial issues) are not represented in the figure. Adapted from [7]. MAR = medically assisted reproduction, ART = assisted reproduction technology, IVF = in vitro fertilization.
Finally, the review revealed a lack of consistent association between any socio-demographic (e.g., age, education), infertility (e.g., years infertile, prior live birth) or clinical (e.g., number and quality of oocytes and embryos) predictors recorded in medical charts at the start of treatment and discontinuation 12 months later.
More recently, a substantial body of research on Patient-Centered Care (PCC) has been focusing on how clinic and organizational factors related to the delivery of treatment may affect compliance behavior. This body of research is based on the assumption that care provided should be tailored to patient’s individual needs, preferences and values. The dimensions of PCC are accessibility, information, communication, patient involvement, respect, continuity and transition in stages of treatment, competence and organization [8]. Cross-sectional research has shown that almost all aspects of PCC are associated with patients’ intentions to comply with treatment [9] and the results of a preference study asking patient to choose between hypothetical scenarios (e.g., slightly lower pregnancy rate but more caring doctor attitude) showed that PCC was an important criteria for choosing and/or changing fertility clinics [10]. However, a prospective study implemented in the Netherlands with 693 infertile women undergoing fertility treatment at 32 different clinics showed that women’s evaluations of PCC did not predict their compliance behavior one year later [21]. Conversely, the patients were not differentiated according to stage of treatment (e.g., diagnostic versus first, second, third cycle) and, as noted, stage determines which reason (including elements of PCC) will be relevant. On going research is examining whether other factors (emotional distress, relational issues) predict compliance.
In conclusion, there are many reasons why patients do not undergo treatment as recommended. A main reason is indefinite postponement and procrastination; patients intend to do it, but do not ultimately do it. The physical and psychological burden of treatment is another common reason, as are relational and personal problems, which may or may not be related to the infertility. Research on the psychology of compliance with ART is not yet mature with many remaining questions concerning the specifics of the broad issues outlined; for example, which relational issues link to non-compliance, when and why. Given the lack of precision on the psychology of compliance in infertility there is also a dearth of studies on patient decision-making in this context. Currently it is known that patients find it stressful to decide about uptake of further treatment [11], especially when they have a very strong wish for children [12]. How this decisional process actually unfolds and who contributes to it (patient, partner [when present], physicians, nurses, etc.) is still not known. Patients themselves express the wish to receive counseling to help them with this decision [13] and 49% think that it should come from their physicians or nurses [14]. Nonetheless, fertility counselors also can play an important role in patient support and understanding during the decision-making process. Ultimately, knowledge from these two different strands (reasons/predictors and decision-making) need to come together if patients are to be better supported in their decision-making process about treatment. The latter is especially important considering the high rates of treatment postponement observed which most likely reflects decisional avoidance.
Enabling compliance from an evidence-based perspective
In the age of EBM, MHPs need to provide psychological care that has demonstrated efficacy, feasibility, cost-efficiency and generalizability [15] in regard to supporting decision-making or addressing the causes of non-compliance in the ART context. In short, practitioners are expected to follow a scientific approach to clinical decision-making and practice [16]. Boivin [15] has discussed extensively the increasing need for fertility counselors to integrate research findings into their everyday practice and has provided MHPs with a framework to meet this challenge using EBM principles. The five steps involved in this process are summarized in Table 19.1. Readers are referred to Sackett et al. [16] for detailed instructions on each step and to Boivin [15] for application in the context of infertility psychological care.
| Step | Description |
| 1 | Convert the need for information into an answerable question. |
| 2 | Track down the best evidence with which to answer that question. |
| 3 | Critically appraise the evidence for its validity (closeness to the true), impact (size of the effect), and applicability (usefulness in our clinical practice). |
| 4 | Integrate the critical appraisal with your clinical expertise and the patient’s unique biology, values and circumstances. |
| 5 | Evaluate your effectiveness and efficiency in executing the previous steps and seek ways to improve them for the next time. |
In the following sections, we apply EBM principles to the compliance issues described in the two case studies presented at the start of the chapter.
Case 1 – Faatina and Balaji: Discontinuation due to poor prognosis
An important reason for ending fertility treatment is anticipated prognosis of the recommended treatment being undertaken. Prognosis is a prediction about the likelihood of a pregnancy (live birth) with continued treatment. Perceived poor prognosis is an important reason why doctors advise patients to end treatment and why patients discontinue treatment. The systematic review presented showed that 15% of patients cited poor prognosis as a reason for discontinuation during first-line fertility treatments (e.g., insemination, ovulation induction) and 30–42% while undergoing ART [6]. In the review, patients perceived that doctors based their prognosis on issues such as a poor response (poor ovarian response, fertilization or embryo quality), absence or inaccessibility of a treatment that could help, and/or medical futility (defined as less than 1% chance of pregnancy [17]). Patients also referred to causes of a poor response (i.e., body mass index > 30 kg/m2, signs of ovarian aging) and inability to correct causes (i.e., failure to lose or gain weight), as per recommendation of the clinic. If patients end treatment because of a genuine poor prognosis, then patients are complying with recommendations.
However, there is evidence that patients perceive a poor prognosis, even when the doctors see a positive outcome. One study observed that 30% of patients who cited poor prognosis as a reason for discontinuation actually had a favorable prognosis according to their doctors, suggesting that patients may lose hope for success before the medical staff do [18] and/or that they define a “poor prognosis” differently. Indeed patients’ stated reasons for discontinuation often refer to aspects such as lack of faith in treatment itself or in the possibility that it would be successful, feeling that success was not meant to be, giving up or simply feeling that all that could be done had already been done [6]. Such statements could corroborate an actual poor prognosis or could reflect patient hopelessness about efficacy of treatment. The fact that clinical indicators of poor prognosis are not significant determinants of compliance (as noted previously [6]) does lend weight to patient perception being a critical aspect for decision-making.
It seems clear that ending treatment due to a poor prognosis can hide different causes, and these need to be identified to select the best psychological support for the patient [4,19]. In particular is the need to counsel patients about the ways they can maximize their chance of success (i.e., adopt healthier lifestyles), how they can maintain hope during treatment, and how they can make the decision to end treatment following a definitive diagnosis of poor prognosis. The first case study presented in this chapter exemplifies the issues fertility counselors may encounter regarding discontinuation due to poor prognosis using EBM principles to identify the best option for support.
Step 1: The need for information is converted into an answerable question
The fertility counselor needs to consider the multifaceted case and select intervention targets consistent with the referral.
The most pressing issue for the medical team is for the patient to receive the necessary psychological support for the problems interfering with compliance. The problematic issues refer to worry about stress, a lack of motivation to achieve weight loss, perceived inability to cope with the stress of the waiting period, which altogether lead to the desire to end treatment despite recommendation to continue. To address these issues, the problems could be translated into the questions that would help the fertility counselor better understand the case and help the patient make an informed decision about pursuing further treatment, which is the subject of referral. The case raises multiple questions:
“In South Asian married women undergoing first-line fertility treatment…
a. …is polycystic ovary syndrome associated with anxiety?
b. …does anxiety decrease the chance of pregnancy?
c. …what are the most effective interventions to reduce anxiety during the waiting period?
d. …are lifestyle interventions effective for weight loss?
The answer to all questions is to some extent necessary to comprehensively understand and address the referral. The first three questions address the beliefs Faatima has about stress, which are reducing her motivation to comply with treatment. The fourth question concerns the issue of effective weight loss interventions, which is a priority area for the healthcare team, but not for Faatima. The fertility counselor can address some or all of these questions depending on resources, relevance to the problem solution, referral and, of course, can only do so if the couple attend for counseling.
Step 2: The best evidence with which to answer that question is identified
The MHP would need to use electronic databases to search for the best evidence for each question.
Some databases require a subscription (e.g., PsychInfo, Web of Science), while others are free (e.g., PubMed, Google Scholar). Free databases can yield relevant information because many authors can be contacted via email to obtain free text reprints of articles identified through the search. In addition, researchers are increasingly choosing to publish via open access, and some scientific journals also choose to make their papers open access after a period of time (e.g., one year for Human Reproduction, the journal of the European Society for Human Reproduction and Embryology). This reduces the disparity in access to information between academic and non-academic professionals. Recent studies comparing the effectiveness of searching via different databases show that Google Scholar out performs PubMed in retrieving twice as many relevant articles and in providing greater access to free-text articles when used by medical doctors [20]. However, skilled indexers may show improved search yields with PubMed [21].
The search terms to be used for the case of Faatima should refer to the problem context (i.e., polycystic ovary syndrome, anxiety, weight loss) but should be combined (in successive order) with terms indicating better quality research designs (e.g., meta-analysis, systematic review) to make the search as effective as possible. See Table 19.2 for quality ratings according to types of designs. The combination of the case and methodology search terms would have identified the following studies of relevance to the case of Faatima and Balaji. First, is a series of meta-analyses examining the prevalence of emotional distress in women with polycystic ovary syndrome [22–25]. Second, are two meta-analyses on the relationship between emotional distress and the outcome of fertility treatments [26,27]. Third, are a systematic review on lifestyle management in polycystic ovary syndrome [28] and a meta-analysis and meta-regression on factors predictive of the effectiveness of weight loss programs [29]. Finally there are a series of randomized controlled trials of coping interventions for the waiting period based on distraction [30,31], positive reappraisal coping intervention [32,33] and telephone support [34]. Overall, 13 studies were identified that could increase case understanding. It should be noted that the process of searching for evidence can be much more complex but is kept to a minimum here for the purposes of illustration. The interested reader is referred to The Cochrane Handbook for Systematic Reviews of Interventions (www.cochrane-handbook.org) [35] for more details of searching for best evidence.
Evidence quality according to type of study design.
| Quality of evidence | Study design | Definition |
| High | Systematic reviews and meta-analysis | The application of strategies that limit bias in the assembly, critical appraisal, and synthesis of all relevant studies on a specific topic. Systematic reviews focus on peer-reviewed publications about a specific health problem and use rigorous, standardized methods for selecting and assessing articles. A systematic review may or may not include a meta-analysis, which is a quantitative summary of the results. |
Multiple randomized control trials Single randomized control trial | An epidemiological experiment in which subjects in a population are randomly allocated into groups, usually called study and control groups, to receive or not receive an experimental preventive or therapeutic procedure or intervention. The results are assessed by rigorous comparison of rates of disease, death, recovery, or other appropriate outcome in the study and control groups. | |
| Large non-randomized trial | A trial in which subjects in a population are non-randomly allocated into groups. | |
| Case control/cohort studies | Cohort-study: The analytic method of epidemiologic study in which sub-sets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of cohort study is observation of large numbers over a long period (commonly years) with comparison of incidence rates in groups that differ in exposure levels. Case control: The observational epidemiologic study of persons with the disease (or other outcome variable) of interest and a suitable control (comparison, reference) group of persons without the disease. The relationship of an attribute to the disease is examined by comparing the diseased and non-diseased with regard to how frequently the attribute is present or, if quantitative, the levels of the attribute, in each of the groups. | |
| Case reports/case series | A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. | |
| Low | Non-analytic studies: Cross-sectional surveys/qualitative | Cross-sectional survey: A study that examines the relationship between diseases (or other health-related characteristics) and other variables of interest as they exist in a defined population at one particular moment (i.e., exposure and outcomes are both measured at the same time). Best for quantifying the prevalence of a disease or risk factor, and for quantifying the accuracy of a diagnostic test. Qualitative study: Data-gathering techniques that are focused on the significance of observations made in a study rather than the raw numbers themselves. |
Definitions adapted from [49]
Step 3: The evidence is critically appraised for its validity, impact and applicability
Critical appraisal is the process by which one judges the trustworthiness of the research being examined.
Critical appraisal varies according to study design (e.g., randomized trial, systematic review, cohort study). The fertility counselor needs to become familiar with the criteria that differentiate good and bad research designs. Although critical appraisal may seem a daunting task at first, many good-quality websites exist to help practitioners do it and once learned the same design quality standards are applied in future appraisals.1 Critical appraisal is a learning experience that will ultimately strengthen the counselor’s confidence in being able to discuss and integrate the very best evidence into clinical practice. A further point to note about appraisal is that it should always include a consideration of fit between evidence and case characteristics.
a. …is polycystic ovary syndrome associated with anxiety?
Four meta-analyses were identified, but the one by Veltman-Verhulst et al. [25] included the earlier reviews, and was therefore the only one examined in greater detail. The review was a comprehensive meta-analysis of comparative studies reporting measures of depression, anxiety or emotional quality of life in women experiencing PCOS. It reviewed 28 studies (2384 patients and 2705 control women) and showed that women with PCOS reported significantly higher emotional distress (anxiety, depression, lower emotional quality of life) than did the comparison control group (other patients, other infertile women, other women with gynecological problems). As Faatima is from South Asia and is married, the review should be examined for information that might be relevant to these specific case characteristics. Marital status was not shown to impact results but studies carried out with American and European participants yielded lower emotional distress scores than did studies with Asian and Australian women. The meta-analysis was conducted according to a very good standard, as per its critical appraisal, and the data were relevant. The conclusions of the review should be examined to identify relevance to the present case. The authors concluded that women with PCOS are at risk for emotional distress and multiple factors could contribute to this distress (e.g., hirsutism, obesity, infertility).
b. …does anxiety decrease the chance of pregnancy?
Two meta-analyses were identified that examined the association between anxiety and outcome of fertility treatment. Boivin et al. [26] reviewed 14 prospective studies including 3583 women undergoing a cycle of in vitro fertilization and concluded no association between pre-treatment anxiety and depression (measured prior to day 5 of stimulation) and the success of a single cycle of IVF (i.e., biochemical or clinical pregnancy rate or live birth rate). In contrast, Matthiesen et al. [27] investigated 31 prospective studies including 4902 women undergoing treatment with assisted reproductive techniques (ART) over single or multiple cycles. The results showed an association between higher emotional distress (perceived stress, life events, occupational or other stress, anxiety and/or depression) and lower pregnancy rates in ART treatment. The reviews are relevant to the case of Faatima, but it should be noted that the samples were infertile women and not specifically women with PCOS. Further, the reviews sampled from many countries, yet none examined country of origin (i.e., South Asia) specifically. Similarly, none of the reviews provided information about marital status and its effect on the association between stress and fertility.
A critical assessment of the two meta-analyses suggests that one should be more cautious about the outcome of the Matthiesen et al. review [27]. The main difference and reason why is because the timing of the psychological and reproductive assessments in the Boivin review were better controlled, avoiding the possible confounding of factors such as poor prognosis and age. Given these confounds, the results of the Boivin review should be prioritized. Boivin et al. [26] concluded that emotional distress levels at the start of one IVF/ICSI cycle are unlikely to affect the outcome of that cycle. Additionally, the authors concluded that anxiety and depression should nevertheless be addressed to improve quality of life during treatment.
c. …what are the most effective interventions to reduce anxiety during the waiting period?
There were no meta-analyses or systematic reviews on coping interventions for the waiting period. Three randomized controlled trials (RCTs) were reported for waiting periods in infertility and cancer patients. Two RCTs considered the impact of active distraction in patients waiting for the outcome of a risk assessment for familial cancer [30,31]. These RCTs showed that an active distraction coping intervention (ADCI), teaching on the benefits of distraction, could reduce intrusive thoughts about risk assessment during the waiting period, but only in people who already had intrusive thoughts to begin with. There was no effect on general emotional distress, avoidant ideation (trying not to think of assessment) or emotions specific to risk assessment (e.g., fear, hope). Although this technique shows promise, a generalizability study in infertile patients facing the ART waiting period has not yet been performed.
The two other RCTs concerned a positive reappraisal coping intervention [32]. The Positive Reappraisal Coping Intervention (PRCI) was conceptualized using the cognitive model of stress and coping [36] and was designed specifically for the waiting period in fertility medical treatment [32,33,37]. The PRCI is a small laminated card that contains ten positive reappraisal statements and a leaflet with a detailed explanation about this coping approach. The ten statements were designed to stimulate the use of positive reappraisal coping techniques (e.g., “Focus on the positive aspects of the situation,” “Focus on the benefits and not just the difficulties,” “Make the best of the situation”). The leaflet describes the challenges of the waiting period and the expected benefits of using positive reappraisal techniques and provides instruction on using the PRCI card. The acceptability, feasibility [32] and effectiveness [32,33] of the PRCI in the waiting period of fertility treatment has been established in several randomized trials [32,33]. These studies also show that the main impact of PRCI is to help women sustain a more positive outlook during treatment (positive emotions, challenge appraisals, more positive reappraisal coping) which makes the stress of the waiting period seem more tolerable even when negative emotions such as tension and worry remain (i.e., helps them carry on). The critical appraisal of these RCTs shows some caution is required due to small sample size [32] or lack of double-blinding [33]. The authors concluded that PRCI could be a low cost way of providing additional support to women by making the two-week waiting period more tolerable. A final RCT of another intervention specific to the waiting period examined the effectiveness of two support telephone calls from a social worker after embryo transfer compared to routine care [34]. Although it was rated as helpful by 66% of those receiving the calls, there was no impact on perceived stress scores. Although there was no analysis of marital status or ethnicity in these trials, the randomization ensured that the groups were equivalent on these factors.
These RCTs are relevant insofar as they provide evidence of the effectiveness of interventions during the waiting period in helping to reduce intrusive thoughts (in cancer context only) or sustain a positive outlook. However, their fit to the specific case of Faatima will depend on whether the counselor believes Faatima needs a reduction in anticipatory anxiety or help to manage an unavoidable emotional state (i.e., waiting is stressful).
d. …are lifestyle interventions effective for weight loss?
Fertility counselors are often asked to assist with behavior change interventions in clinics. A Cochrane systematic review of RCTs comparing lifestyle treatment to minimal or no treatment in women with PCOS was identified [28]. The review was performed on 6 studies (including 164 women). A meta-analysis could not be performed because the lifestyle interventions differed between studies (diet, exercise, behavior management techniques, or combined interventions). The lifestyle interventions were associated with reductions in weight (about 3.5 kg/7.7 lb. weight loss for programs of about six months) and waist circumference (about 1.95 cm/ .8 in. loss). However, there was insufficient data to conclude whether these had an impact on reproductive outcomes (i.e., pregnancy, live birth, miscarriage, ovulation or menstrual regularity) because too few or no studies examined these outcomes. Moreover, it was not possible to examine variations in these effects according to characteristics of the interventions (e.g., duration, content, motivational interviews) because too few studies used the same intervention. The systematic review is relevant to the case but some caution needs to be exercised because the interventions were heterogeneous and it was not possible to identify the cause of heterogeneity. There was no detailed analysis of country of origin or marital status. Moran et al. [28] concluded that interventions were effective to improve body composition (weight, waist circumference) in women with PCOS without evidence to conclude on reproductive outcomes.
A second meta-analysis was identified in the search, though this meta-analysis was not specifically with patients that had PCOS [29]. A primary question of that review was about the factors that predicted the most effective weight-loss interventions. The systematic review and meta-analysis was of RCTs of multicomponent behavioral weight management programs in overweight and obese adults with at least one follow-up at 12 months. The review included 37 studies (> 16 000 participants). The overall weight loss was lower than that reported in Moran et al. [28] and was 2.8 kg/6.2 lb at the minimum 12-month assessment. The meta-regression controlling for all factors simultaneously showed that the intervention components that remained significantly associated with weight loss were calorie counting, contact with a dietitian and the use of behavior change techniques that allowed participants to compare their behavior to that of others (e.g., information about others’ approval, information about normative behavior, modeling or behavior demonstrations, and/or facilitating social comparisons) [29]. There was no evidence that supervised physical activity or more frequent in-person contact had an impact on the effectiveness of the program [29].
The meta-analysis [29] is relevant to the case of Faatima because it shows the effect of weight loss programs and because knowledge of predictors of effectiveness could help Faatima choose the most effective program. The critical appraisal suggests some caution because some of the comparisons reported were based on a small number of studies and some results (e.g., usefulness of calorie counting) could be confounded by other uncontrolled intervention differences (e.g., use of a self-monitoring device). Further the generalizability to patients with PCOS is not known. The authors concluded that most behavioral interventions were effective in reducing weight, but that some interventions were better than others (as described).
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