Psychosocial risks associated with multiple births resulting from assisted reproduction

Psychosocial risks associated with multiple births resulting from assisted reproduction Marcia A. Ellison, Ph.D.,a,e Selen Hotamisligil, M.D., Ph.D.,d Hang Lee, Ph.D.,b Janet W. Rich-Edwards, Sc.D.,c Samuel C. Pang, M.D.,d and Janet E. Hall, M.D.a a Reproductive Endocrine Unit and b Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; c Department of Ambulatory Care and Prevention, Harvard Pilgrim Health Care and Harvard Medical School, Boston, Massachusetts; d Reproductive Science Center, Lexington, Massachusetts; and e RAND Corporation, Santa Monica, California

Objective: To determine if increased psychosocial risks are associated with each increase in birth multiplicity (i.e., singleton, twin, triplet) resulting from assisted reproduction. Design: Stratified random sample (n ⫽ 249). Setting: An academic teaching hospital and private practice infertility center. Patient(s): Mothers raising 1- to 4-year-old children (n ⫽ 128 singletons, n ⫽ 111 twins, and n ⫽ 10 triplets) conceived through assisted reproduction. Intervention(s): Self-administered, mailed survey. Main Outcome Measure(s): Scales measuring material needs, quality of life, social stigma, depression, stress, and marital satisfaction. Result(s): Using multivariate logistic regression models, for each additional multiple birth child, the odds of having difficulty meeting basic material needs more than tripled and the odds of lower quality of life and increased social stigma more than doubled. Each increase in multiplicity was also associated with increased risks of maternal depression. Conclusion(s): To increase patients’ informed decision-making, assisted reproduction providers might consider incorporating a discussion of these risks with all patients before they begin fertility treatment, and holding the discussion again if the treatment results in a multiple gestation. These data may also help providers to identify appropriate counseling, depression screening, and supports for patients with multiple births. (Fertil Steril威 2005; 83:1422– 8. ©2005 by American Society for Reproductive Medicine.) Key Words: Multiple births, fertility treatment outcomes, depression, quality of life, iatrogenic, twins, triplets

Assisted reproductive technology (ART) has been the key contributing factor in the 49% increase in twin birth rates, and the 423% increase in higher order multiples in the United States over the past 30 years (1–3). The maternal and child medical risks independently associated with ART and multiple births have been documented (4 –11), as have the economic impacts of multiple births on hospital charges (12, 13). To date, relatively few studies have examined the psychosocial risks (e.g., quality of life, depression, social stigma) incurred by families whose ART treatment resulted in multiple birth children (14 –16). To more fully address this issue, we recently identified the quality of life (QOL) domains that are most affected by multiple births (17). That study, however, did not quantify these outcomes, nor did it examine how decrements in QOL in ART multiple birth families might increase as the type of multiplicity increases (i.e., twins, triplets).

Received August 16, 2004; revised and accepted November 23, 2004. Supported by the Harvard Medical School Center of Excellence in Women’s Health, and NIH T32HD 07396, K24HD 10290, and M01RR 1066. Reprint requests: Marcia A. Ellison, Ph.D., RAND Corporation, 1776 Main Street, Santa Monica, CA 90407 (FAX: 310-451-7004; E-mail: ellison@ rand.org).

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Studies suggest that the infertility experience influences family QOL, regardless of whether the pregnancy resulted in a singleton or more (18 –24). For example, in ART singleton families, the experience of infertility was associated with enhanced parenting satisfaction (18 –22) but was also found to increase maternal stress and decrease maternal self-efficacy (23, 24). Studies of ART twin families found greater parenting stress and decreased parenting satisfaction (14, 15) compared with families raising spontaneously conceived twins. Collectively, these studies suggest that the infertility experience increases families’ psychosocial vulnerabilities. In contrast, a study had found no significant difference in parenting stress among singleton mothers treated with in vitro fertilization (IVF) and mothers of singletons conceived spontaneously; however, at 1 year postpartum, IVF multiple birth mothers were found to have significantly higher parenting stress and reported higher rates of feeling depressed than their singleton IVF counterparts (16). Given these findings, and the protracted discussion and concern among fertility treatment providers about multiple birth outcomes, it is particularly critical that the psychosocial impacts of this treatment outcome are more fully understood (25–29).

Fertility and Sterility姞 Vol. 83, No. 5, May 2005 Copyright ©2005 American Society for Reproductive Medicine, Published by Elsevier Inc.

0015-0282/05/$30.00 doi:10.1016/j.fertnstert.2004.11.053

Our current study was designed to control for the infertility and treatment experience, to determine if QOL outcomes among ART families are associated with increased multiplicity. We used the ability of a family to meet its material and psychosocial needs as indices of QOL. Thus, we measured a broad range of outcomes, including difficulty meeting material needs, global QOL, perceived social stigma, depression, stress, and marital satisfaction. MATERIALS AND METHODS Study Population We identified survey respondents through medical records from two sites, the Reproductive Science Center, a private infertility treatment clinic in Lexington, Massachusetts, and an ongoing obstetric study at Massachusetts General Hospital in Boston. We limited the survey to mothers whose children had been conceived as the result of ART, defining ART as any medically mediated conception that included ovulation-enhancing medication, with or without a reproductive technology such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). We classified participants into three comparison groups by their treatment outcomes of singleton, twin, or triplet birth. To avoid capturing postpartum depression, which typically abates within 1 year, the children of all participants were at least 12 months old. We also excluded mothers whose children were over 48 months of age, thus limiting the study to preschoolers. All participants resided in New England and were treated in Massachusetts. We stratified the study population into two strata of singleton mothers and multiple birth mothers. We then seeded these samples with random numbers and used the lowest random numbers to identify the singleton sample and then to match singleton mothers to multiple birth mothers by children’s year of birth, maternal age, and parity status. The Partners Human Research Committee and the Massachusetts General Hospital’s Mallinckrodt General Research Council approved the study. A completed, returned survey constituted informed consent. All responses were anonymous. Survey Data Collection The mailed, self-administered survey was designed from a review of the literature and from the findings of our previous focus group research identifying the core QOL concerns of ART singleton and multiple birth mothers (17). The pretested and revised survey instrument included validated scales, supplemented as necessary with two scales developed from the findings of our qualitative study, and revisions to a marital satisfaction scale to reflect the key marital satisfaction concerns of those study participants (17). The face and content validity of the scales that we had developed to measure material family needs, social stigma, and marital satisfaction were ensured through focus group pretests with ART mothers as well as through group and one-on-one interviews with experts in reproductive medicine. The tests of the internal validity of each of these scales were acceptFertility and Sterility姞

able. The surveys, mailed in a survey packet with a cover letter and a stamped return envelope, included the following QOL assessments. Meeting material family needs. We used the material needs identified in our previous study (17) to develop a 10-item scale to measure the degree of difficulty in meeting the following material needs over the previous 12 months: food, clothing/shoes, equipment, supplies, transportation, housing, childcare assistance, activities and classes, education, and health care needs. A 4-point scale measured responses from 0 “not difficult,” to 1 “somewhat difficult,” to 2 “moderately difficult,” to 3 “very difficult.” Scores ranged from 0 to 30, with higher scores representing increased unmet material need; Cronbach’s alpha was 0.86. Social stigma. Our previous focus group study documented increased social stigma among multiple birth mothers compared with their singleton counterparts (17). Thus, we developed a 4-point scale to measure whether respondents felt that, because of their use of ART, [1] people viewed their family as “unnatural,” [2] people asked them invasive questions, [3] their family experienced social stigma, or [4] they felt different from women who had conceived spontaneously? Responses varied from 0 “not at all,” to 1 “not often,” to 2 “fairly often,” to 3 “very often.” Scores range from 0 to 12, with higher scores indicating higher levels of social stigma. Data were analyzed for both the 4-item scale and for the two questions that directly addressed the issue of social stigma (i.e., family stigma, family perceived as “unnatural”). Cronbach’s alpha for the 4-item scale was 0.72. Overall quality of life. The 32-item Ferrans and Powers Quality of Life Index (30) was used to measure global QOL (we excluded one item that was inappropriate for this study). The scale uses an algorithm to establish a 6-point rating of satisfaction for each item (from very, moderately, or slightly dissatisfied to slightly, moderately, or very satisfied) as well as a 6-point rating of the importance of each item (from very, moderately, or slightly unimportant to slightly, moderately, or very important). Global scores ranged from 0 to 31, with higher scores indicating greater satisfaction with QOL. This validated scale (30) has high internal consistency in surveys of pregnant and postpartum women, Cronbach’s alpha was .96 and .89, respectively (31), and test–retest reliability at 2 weeks was good (r ⫽ .87). Marital satisfaction. We modified the Kansas Marital Satisfaction Scale (KMSS) (32) to include and measure the core concerns of the mothers in our previous study, addressing issues relevant to couples raising young children. We eliminated one of the three KMSS variables, “how satisfied are you with your relationship with your husband,” and added five items identified in our previous study as important to marital stability (17). These included the level of satisfaction with the husband/partner’s communication, emotional support, help with childcare, help with daily household tasks, and parenting style. Each item was measured on a 4-point scale that ranged from 4 “extremely satisfied,” to 3 “some1423

FIGURE 1 Prevalence (%) in outcomes by multiplicity in full-term births: purple ⫽ singletons; green ⫽ twins; turquoise ⫽ triplets. *P ⬍.05, **P ⬍.001. **

Increased Difficulty Meeting Needs

Outcomes

* Decreased

Quality of Life

* Increased *

Social Stigma

Increased Depression Increased Stress

Decreased Marital Satisfaction

0

10

20

30

40

50

Percent of Prevalence Ellison. Psychosocial risks of multiple births. Fertil Steril 2005.

what satisfied,” to 2 “somewhat dissatisfied,” and to 1 “extremely dissatisfied.” Scores ranged from 7 to 28, with higher scores indicating greater marital satisfaction; Cronbach’s alpha was 0.90. Stress. We used the validated 10-item Cohen Perceived Stress Scale (33) to measure the sense of a lack of control, unpredictability, and emotional or task overload. Total scores range from 0 to 40; higher scores indicate greater levels of perceived stress. This validated scale has a Cronbach’s alpha coefficient of .78, with a high 2-day test–retest correlation (0.85) (33). Depression. To measure maternal depression, we used the 20-item Centers for Epidemiological Study-Depression Scale (CES-D) (34). Scores ranged from 0 to 60, with higher scores indicating greater distress. We selected this scale to facilitate comparisons with previous studies of depression among multiple birth mothers (35, 36). This scale has been widely used and validated in studies of the general population, with good internal consistency (0.84) and test–retest reliability. Children with Health/Developmental Problems We used a binary measure to determine children’s health status, “Has your child/ren had any health or developmental problems?” Statistical Analyses We used chi-square tests and Kruskal-Wallis tests to determine if there were statistically significant differences in 1424

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demographic characteristics by type of multiplicity. Raw scores for each scale were dichotomized, using the 10th or 90th percentiles as cutoff points, to designate psychosocial outcomes. Thus, we considered women scoring above the 90th percentile of the material needs, social stigma, or the stress scales to have high-scored outcomes. In contrast, women scoring below the 10th percentile of the QOL index or the marital satisfaction scales were considered to have low-scored outcomes. The validated CES-D threshold of ⱖ16 was used to indicate the risk of maternal depression (34). We used separate multivariate logistic regression models to estimate the odds ratios and 95% confidence intervals for each outcome by multiplicity (Fig. 1). We modeled multiplicity as a continuous term (singleton ⫽ 1; twin ⫽ 2; triplet ⫽ 3). Reported P values are two-sided; P ⬍.05 was considered statistically significant. All analyses used SPSS version 8.0 (SPSS, Inc., Chicago, IL). RESULTS The survey included mothers (n ⫽ 249) of 128 singletons, 111 twins, and 10 triplets, with an overall response rate of 64%. The response rate was higher among multiple birth mothers (77%) than singleton birth mothers (52%). At the time of their children’s birth, the mean maternal age was 35 (⫾ 4 standard deviations [SD]); their children’s current mean age was 22 months (⫾ 8 SD). The demographics of the survey participants (Table 1) mirror national demographics of women who seek fertility treatment, who tend to be affluent, well educated, and white Vol. 83, No. 5, May 2005

TABLE 1 Demographic characteristics of survey respondents, by multiplicity. % Prevalence Characteristic

Overall (n ⴝ 249)

Singleton (n ⴝ 128)

Twin (n ⴝ 111)

Triplet (n ⴝ 10)

72 19

73 17

73 22

60 30

2

⬍1

5

0

92 4 3 ⬍1 ⬍1

91 5 3 ⬍1 0

93 3 3 0 1

80 20 0 0 0

60 40 35

60 40 36

62 38 35

40 60 20

16 46 38

16 44 40

15 51 34

30 30 40

Primipara Children with health/developmental problem Current marital status Divorced/separated Ethnicity White Asian/Pacific Islander Latina/Hispanic African American/Black American Indian/Alaska Native Education Less than 4 years of college At least 4 years of college Advanced degree Income ⬍$60,000 $60,000–119,999 ⬎$120,000 Ellison. Psychosocial risks of multiple births. Fertil Steril 2005.

(37). For example, compared with the median household income in the United States of $46,000, only 15% of the survey respondents had pretax annual incomes under $60,000, and 35% had an advanced degree. Comparisons by multiplicity also indicated that there were no statistically significant differences between the three groups in maternal education, pretax household income levels, ethnicity, or maternal age. As expected, multiple birth children had greater health and developmental problems than their singleton counterparts (17% singletons, 22% twins, 30% triplets), but as these differences were not statistically significant we did not include covariates in our multiplicity model. For the majority (72%) of the respondents, this was their first fullterm pregnancy. Their ages at the time of their children’s births ranged from 25 to 49 years, with median age of 35 years. The data suggest that ART multiple births result in psychosocial risks that increase by multiplicity (Table 2; also see Fig. 1). Using multivariate logistic regression models, for each additional multiple birth child, the odds of having difficulty meeting basic material needs more than tripled (OR 4.74, 95% CI: 2.23–10.09), while the odds of lower quality of life (OR 2.45, 95% CI: 1.16 –5.15) and increased social stigma (OR 2.08, 95% CI: 1.11–3.91) more than doubled. Each increase in multiplicity was also associated with increased risks of maternal depression (OR 1.71, 95% CI: 1.00 –2.92). In addition, we separately examined the two items directly measuring social stigma (i.e., Fertility and Sterility姞

family stigma, “unnatural” family) and found statistically significant increases in social stigma which increased by multiplicity (P⬍.05, OR 1.68, 95% CI: 1.01–2.82; 18% singletons, 26% twins, 40% triplets). The decreases in marital satisfaction, although not statistically significant, were consistent with each additional increase in a multiple birth child. DISCUSSION This study elucidates the psychosocial risks associated with iatrogenic multiple births, and suggests that these risks increase with each additional multiple birth child. These risks include significant difficulty in providing basic material needs for their families, decreased quality of life, and increased risks of social stigma and maternal depression. The identification of these risks may be helpful in counseling those seeking fertility treatment, as patients may underestimate the difficulties involved in raising multiple birth children, or may understand the risks associated with triplets but be naïve with respect to twins (38 – 40). Part of the problem with patient understanding may also be due to a lack of awareness among providers about the medical risks (e.g., neonatal encephalopathy, cerebral palsy) of multiple births (41) as well as the psychosocial risks identified in our recent research. There has been anecdotal evidence of increased difficulty in meeting basic material needs among multiple birth families (42). Peer support groups for multiple birth mothers have 1425

TABLE 2 Prevalence and odds ratios for social risks associated with incremental increases in multiplicity in assisted reproduction births. Odds ratio per increased multiple birth infant

% Prevalence Singleton (n ⴝ 128)

Outcomes Difficulty meeting material needs Lower quality of life Social stigma Maternal depression Maternal stress Lower marital satisfaction

Twin (n ⴝ 111)

Triplet (n ⴝ 10)

Point estimate

CIa

2.4

18.2

30

4.74b

(2.23–10.09)

4.7 7.9 15.9 7.1 7.8

12.1 18.2 22.9 13.8 11.8

20 20 40 10 22.2

2.45c 2.08c 1.71c 1.65 1.65

(1.16–5.15) (1.11–3.91) (1.01–2.92) (0.83–3.29) (0.82–3.31)

a

95% confidence interval. P ⬍.001. c P ⬍.05. b

Ellison. Psychosocial risks of multiple births. Fertil Steril 2005.

long been aware of this unmet need, which they formally address by creating mechanisms to recycle equipment (e.g., specialized strollers, car seats), clothing, formula, food, and by sharing information to help these families access existing public support programs (Triplets Moms and More, personal communication to Ellison). Churches and community organizations may also offer informal ad hoc support to multiple birth families, providing food, clothing, and childcare (Triplets Moms and More, personal communication to Ellison). However, no studies to date have systematically quantified this outcome. This study suggests that, in spite of their socioeconomic advantages, ART multiple birth families face greater difficulties in meeting their basic material needs than their singleton counterparts. In addition to the increased difficulty ART multiple birth families may face in meeting their basic material needs, the decrements in global QOL associated with this outcome indicate that these families may require formal social supports. Because of the cross-sectional design of this study, we were not able to determine which kinds of social supports might be most useful across children’s developmental trajectories. Thus, additional studies will be necessary to identify peaks in these needs and QOL risks across children’s developmental stages. These data would help shape appropriate health and social policies to ameliorate these stressors and improve QOL in these vulnerable families. Understanding how these needs may escalate or decrease across time would also help treatment providers ensure their patients receive appropriate and timely care. Social stigma, which encompasses myriad forms of spoiled or damaged identity (43), has received only cursory attention in studies of infertility or ART multiple births (44). Thus, this 1426

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outcome was a novel finding in our previous study (17). In this current study we have quantified the stigma associated with multiple births. Mothers of ART multiple birth children reported feeling significantly more socially marked and devalued by their treatment decision than their singleton counterparts. This finding identifies an area of psychological counseling that could be integrated into existing counseling services in infertility clinics. Patients could be counseled to anticipate and effectively cope with questions about their fertility treatment, as well as the moral recriminations and other forms of stigma they may encounter, which were reported by all ART multiple birth mothers in the research that informed our current survey (17). These qualitative data suggested that a multiple birth exposes women to unwanted public speculations and intrusive questions about their fertility status and their children’s conception status. A form of peer training could also become a focal topic for the support groups that mothers have forged in response to increasing multiple birth outcomes from assisted reproduction in the United States. Previous studies have reported high rates of depression in mothers of twins (45) and triplets (35, 36). Using the same well-validated scale, our research was able to document that maternal risks of depression increased significantly by multiplicity. These findings support early research on the psychosocial consequences of multiple births (46) that proposed the psychological burden of raising more than one infant at the same developmental stage put mothers at risk of exhaustion and depression. Moreover, qualitative data from our earlier study suggest that the guilt that multiple birth mothers reported about feeling overwhelmed or depressed after seeking ART may decrease their willingness to seek help or admit their distress to their physician (17). Vol. 83, No. 5, May 2005

Our current findings underscore the importance of pediatricians, family practitioners, and gynecologists being vigilant in referring or routinely screening ART multiple birth mothers for depression. Further studies will be required to determine optimal supports for reducing multiple birth mothers’ risk of depression and to determine the best approaches to help destigmatize depression and encourage treatment seeking for women who have been through the infertility and treatment experiences.

ing multiple births (25–29). The reduction in higher order multiple births in the United States since 1997 suggests that shifts in practice can reduce multiple births (47); however, mandating health insurance coverage for fertility treatment does not appear to be sufficient, in and of itself, to decrease multiple birth rates (48 –50). As importantly, there is currently a lack of accord among providers regarding regulatory standards for the number of embryos transferred or formal reporting of ovulation induction treatment (25–29, 51–53).

This study has several limitations. While the 64% response rate was high for a “cold” mailed survey, the responses were greater among multiple birth mothers (76%) than singleton mothers (52%). As evidenced in our previous findings, multiple birth mothers may have participated at a higher rate in the hope of sharing their experience with others (17). This would bias the survey only if multiple birth mothers with negative experiences were more likely to respond than those with positive experiences.

Government regulation in many European nations that limit the number of embryos transferred appear to be responsible for the 50% lower rate ART multiple births compared with the United States (54). Reducing the number of embryos transferred can effectively reduce multiple gestations without significantly reducing live birth rates for some patients (51, 52). However, externally imposed state or federally regulated reproductive policies may fail to take into account that younger women are at greater risk of ART multiple births than older women (1–3), and that meeting the goal of a live term singleton for patients with specific characteristics may necessitate the transfer of multiple embryos. Therefore, self-regulated policy and practice changes from both the medical and health policy communities to reduce ART multiple births, that take these factors into account by limiting the number of embryos transferred by specific patient characteristics, may eventually be necessary to avoid having uniform limitations imposed externally by governmental regulatory bodies.

Other limitations include the use of a scale developed from our previous research to measure maternal perceptions of the social stigma associated with ART. This scale needs to be further tested in future research. It is important to note that our previous qualitative work suggests that the invasive questions and sense of being different from other women that we identified in that research were not perceived positively or as a “celebrity status” by mothers who had experienced infertility and whose children were conceived through ART. In addition, the binary maternal self-report measure of children’s health is not a sensitive or specific measure of maternal perception of child health, and it is possible that the inclusion of more detailed measures might have reduced some of the odds ratios associated with multiplicity. However, as multiplicity and consequent preterm birth and low birth weight are often the cause of the health problems, controlling for child health status may be overcontrolling for an intermediate, pathway variable. Although the survey was informed by qualitative research, the potential of all self-report scales to overrepresent or underrepresent levels of psychological distress underscores the importance of integrating in-depth interviews in future survey research with this population. The cross-sectional design is a limitation of this study and future studies should be designed to follow patients longitudinally, from the diagnosis of infertility onward, to more clearly identify and predict the long-term psychosocial risks of ART multiple births. Inclusion of fathers is also an important area of study for future research. Finally, this study compared outcomes in families who had received fertility treatment; further studies will be required to determine whether these results can be generalized to spontaneously conceived multiples. This study’s findings also have implications for treatment policy and practice guidelines, and contribute to the on-going dialogue among fertility treatment providers about the American Society of Reproductive Medicine (ASRM) goal of reducFertility and Sterility姞

In conclusion, the significant psychosocial risks associated with each increase in the number of ART multiple birth children include difficulty in providing basic material needs for their families, lower QOL, and increases in social stigma and maternal depression. The identification of these risks can provide useful information in counseling those seeking fertility treatment, who may underestimate the difficulties involved in raising multiple birth children. Future prospective studies are needed to test these findings. If our findings are replicated, this may also help assuage the unease that some providers may feel in having a frank discussion with their patients about the psychosocial risks associated with ART multiple births (38). Fertility treatment clinics, the common point-of-service contacts for families with ART multiple gestations, have a unique opportunity to develop continuity of care guidelines for counseling and support services that could ameliorate the psychosocial risks related to this still common treatment outcome. Acknowledgments: The authors thank the women who participated in this study; Ravi Thadani, M.D., Massachusetts General Hospital, for his help in identifying potential participants; and the reviewers for their helpful comments.

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Vol. 83, No. 5, May 2005