1 St Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, 2 University Medical Centre, Heidelberglaan 100, 3584 CX, Utrecht, 3 St Elisabeth Hospital, Hilvarenbeekseweg 60, 5022 GC, Tilburg, 4 Tweesteden Hospital, Dr Deelenlaan 5, 5042 AD, Tilburg and 5 Maxima Medical Centre, de Run 4600, 5504 DB, Veldhoven, The Netherlands
6 To whom correspondence should be addressed. Email: p.graziosi{at}antonius.net
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: curettage/early pregnancy failure/misoprostol/quality of life
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Only one study compared psychological well-being, depression, anxiety and satisfaction in women treated with misoprostol as compared to curettage (Lee et al., 2001). No difference in psychological well-being was observed. However, since the study was conducted in China, the authors stated that due to cultural differences these outcomes might not be applicable in Western society.
Recently, we performed a randomized clinical trial comparing misoprostol and curettage in women with early pregnancy failure who had been managed expectantly for 1 week after the initial diagnosis (Graziosi et al., 2004
). According to our findings, misoprostol treatment is expected to lead to a high percentage (47%) of women who need curettage as well. Moreover, women treated with misoprostol experienced evacuation at home and both severity of bleeding and pain were increased in these women as compared to curettage.
Since, apart from clinical effectiveness, quality of life should be taken into account when deciding for a particular treatment, we assessed health-related quality of life and patients' satisfaction alongside our randomized clinical trial.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Curettage treatment consisted of evacuation of the uterus by suction curettage under general anaesthesia in a day care setting.
Misoprostol treatment (four tablets of 200 mg administered vaginally, repeated after 24 h in cases of incomplete abortion) was given after randomization in an outpatient setting. Participants were allowed to use analgesic medication.
Misoprostol treatment was considered to have failed when curettage was needed. Criteria for the need of curettage were: presence of abnormal bleeding and signs of retained products of conception >3 days following misoprostol administration (i.e. presence of gestational sac or a focal hyperechoic intrauterine mass with an anterior posterior diameter >15 mm at ultrasonography), profuse bleeding or infection.
Similarly, curettage was considered to have failed when intervention was needed because of abnormal bleeding and signs of retained products of conception visible at ultrasonography.
Health-related quality of life was assessed with the use of standard self-administered psychometric measures with established reliability and validity. We used the Short Form 36 (SF36), the StateTrait Anxiety Score (STAI) and the Self-rating Depression Scale (SDS) (Zung, 1965; Stewart, 1988
; de Vries, 1994
; van der Ploeg, 2001
).
The generic SF36 compromises seven subclasses: physical functioning, role functioning, social functioning, mental health, vitality, pain and health perception. Physical functioning refers to limitations in a variety of physical activities ranging from strenuous to basic (e.g. carrying groceries, climbing stairs and self-care). Role functioning and social functioning refers to limitations in common daily or social activities resulting from health problems (e.g. working, attending school or visiting friends). Mental health was assessed in terms of psychological distress and well-being. Vitality was measured using a scale for energy, and pain was measured using a pain scale. Health perception refers to patients' overall ratings of their current health in general. The subscales were transformed to a 0100 scale, with higher scores indicating better quality of life.
Anxiety was measured with the STAI, which measures both state and trait anxiety. State anxiety refers to momentarily experienced anxiety. Trait anxiety refers to the general tendency of an individual to be anxious, and is considered a personality trait. We measured trait anxiety at the start of the study and state anxiety at baseline and at subsequent follow-up. The SDS was used to measure depression. This scale measures the subjective experience of depression as characterized by affective, cognitive, behavioural and psychological symptoms.
Client satisfaction and acceptance of the mode of treatment were assessed 2 weeks after treatment, using a questionnaire derived from the Client Satisfaction Questionnaire (Larsen et al., 1979). Three items were used including overall rating of satisfaction with the medical service, satisfaction with recovery after treatment and whether they would choose the same treatment in the future.
In order to compare treatment effects on health-related quality of life, assessment was made at four points in time. The first set of questionnaires was completed immediately after randomization. Women received a further three sets of questionnaires which were completed after 2 days, 2 weeks and 6 weeks after allocated treatment. All questionnaires were returned in sealed envelopes.
Data analysis
Health-related quality of life was studied on an intention-to-treat basis. Repeated measures analysis of variance were used to establish changes in health-related quality of life over time (time effect), differences in health-related quality of life between both treatment groups (treatment effect) and interaction between changes in health-related quality of life over time and treatment (time by treatment effect) (Hays, 1998).
Women with missing measurements were included in the repeated measurement analysis if data were available for at least two different time-points (Zwinderman, 1992). P<0.05 was considered to indicate statistically significant differences. If statistically significant differences in health-related quality of life between both treatment groups or an interaction between changes in health-related quality of life over time and treatment group was found, Student's t-test was used to examine differences between treatment groups at specific time-points. As trait anxiety was measured only once, Student's t-test was used for analysis. In an additional analysis, we compared the health-related quality of life in women in whom misoprostol was successful to women in whom misoprostol did not lead to complete evacuation and curettage was also needed.
The sample size calculation was based on a difference in complete evacuation rate (Graziosi et al., 2004). As only one outcome can be the primary one, and sample size has to be based on this outcome, the number of patients included in the study is based on this power. For the SF-36, in order to detect a 10-point difference in the Physical Component Summary scale and Mental Component Summary scale as relevant, two groups of 65 patients are sufficient to find relevant differences (alpha 0.05; beta 0.80; SD 20).
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Emergency curettage was needed in 12 women allocated to misoprostol and two women allocated to curettage.
Seventy-three women allocated to misoprostol (93%), completed at least two questionnaires, as compared to 58 (77%) women allocated to curettage (P=0.007). Baseline characteristics of women who responded and who did not respond are shown in Table I. There were no statistically significant differences between responders and non-responders included in the study with respect to baseline characteristics or treatment allocation. The number of women allocated to misoprostol therapy and curettage who completed health-related quality of life measures at separate time-points for misoprostol and curettage were 73 versus 58 after randomization, 71 versus 57 after 2 days, 68 versus 55 after 2 weeks and 61 versus 48 after 6 weeks respectively.
|
|
|
Failed misoprostol compared to successful misoprostol
Differences in health-related quality of life were more profound and statistically more often significant for more dimensions in women with failed misoprostol as compared to women in whom misoprostol was successful (Figure 3, Table III).
|
|
After 6 weeks, physical functioning (P=0.05), social function (P=0.02), mental health (P=0.03), vitality (P=0.006), bodily pain (P=0.02) and general health (P=0.003) were still impaired in women in whom misoprostol had failed as compared to women in whom misoprostol caused complete evacuation.
For physical function and mental health, a statistically significant interaction between changes in health-related quality of life over time and treatment group was found, indicating a longer period of recovery in women in whom misoprostol had failed.
StateTrait Anxiety Inventory
There were no statistically significant differences between both treatment groups in trait or state anxiety (Figure 4, Table II).
|
Depression Scale
Women in both treatment groups were equally depressed at baseline (Figure 4, Table II). Two weeks after treatment, depression had decreased to levels within the normal range in both treatment groups. A statistically significant interaction between changes in health-related quality of life over time and treatment group was found, which was due to a slightly slower recovery in the curettage group.
Client satisfaction and acceptance
The two groups were not significantly different in terms of satisfaction with hospital service (Table IV). Women treated with misoprostol were less satisfied with their recovery after treatment as compared to women allocated to curettage. In terms of satisfaction with recovery and hospital service, participants allocated to the misoprostol strategy were equally satisfied with recovery as compared to women allocated to curettage.
|
Participants who required curettage after a failed misoprostol treatment were equally satisfied with the hospital service and recovery as compared to women in whom misoprostol treatment caused complete evacuation. However, when asked whether they would choose a misoprostol treatment in the future, this choice depended on the initial success of misoprostol: when misoprostol had caused complete evacuation, 76% of the women would opt for the same treatment, whereas only 38% of women who needed curettage after failed misoprostol would do so (P<0.01) (Table IV).
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Only one other study comparing misoprostol to curettage in treatment of early pregnancy failure reported on psychological well-being (Lee et al., 2001). In that study, 218 women were randomly allocated to curettage or misoprostol. Complete evacuation was achieved in 50% of women treated with misoprostol, and the study showed comparable psychological well-being in both groups. This result is in concordance with our findings.
In addition, measurement of health-related quality of life was worthwhile in our trial showing temporarily declined scores for general health and pain in women allocated to misoprostol. This implies that health-related quality of life measurements provide significant supplementary information in assessing psychological dimensions of a treatment intervention.
Many publications confirm the negative psychological impact in terms of anxiety and depression of early pregnancy failure on a significant proportion of women (Thapar and Thapar, 1992; Neugebauer, 2003
). This was also observed in our study. The results in our study demonstrate that while there were no obvious differences in anxiety and depression scales, there was a significant interaction mainly due to higher anxiety in the curettage group and slower recovery of depression scales in the curettage group.
Our data on patients' satisfaction show that a choice for misoprostol treatment in the future depends on the initial success of this treatment, as almost twice as many women (76%) in whom misoprostol treatment succeeded would choose the same mode of treatment in the future. This speaks for the better acceptability of this non-invasive approach to early pregnancy failure, as long as treatment success is high. Equal patterns on satisfaction rates (i.e. willingness to choose the same treatment in the future) were reported in other studies for women in whom misoprostol resulted in complete evacuation (Demetroulis et al., 2001; Wood and Brain, 2002
).
Our study has some limitations. Thirty-six per cent of the eligible participants were not recruited into the study. It is important to realize that misoprostol was only available for women in the trial. As a consequence, our findings might be biased in favour of misoprostol, since women who opted for curettage and were not willing to be randomized were treated accordingly. In contrast, women who had a prior preference for misoprostol could only obtain this treatment after randomization.
We had a lower non-response rate in the women allocated to curettage as compared to women allocated to misoprostol. There were no significant differences in baseline characteristics in non-responders for both treatment allocations. Moreover curettage was almost always successful, and it is unlikely that health-related quality of life in the curettage group differed between responders and non-responders. Furthermore, and more importantly, the response in the misoprostol group was good and there was no difference in response rate between women in whom misoprostol was successful and women who needed additional curettage.
The 53% complete evacuation rate of misoprostol in our study is slightly lower as compared to the 6088% success rates described in other trials, using comparable misoprostol treatment protocols and criteria for diagnosis of treatment failure (Demetroulis et al., 2001; Muffley et al., 2002
; Wood and Brain, 2002
). The preceeding expectant management and criteria for deciding upon failed misoprostol treatment as used in our study protocol might explain the lower evacuation rate in our study. A recent study by Creinin et al. (2004)
showed that there is no obvious relationship between increasing endometrial thickness and the need for surgical intervention in women treated with misoprostol for early pregnancy failure. It must be noted, however, that in our study incomplete evacuation in the misoprostol group was due either to profuse bleeding or to persistent presence of a gestational sac in the majority of cases (78%). These women clearly needed additional curettage.
Our results on quality of life are not applicable to women who have been treated immediately after diagnosis of early pregnancy failure or with other criteria on diagnosis of incomplete abortion after initial misoprostol treatment with consequently possible higher complete evacuation rates.
The present study showed an effect on women's health-related quality of life after both treatments. Misoprostol had a temporarily more negative effect on health-related quality of life, which is explained by the experience of an abortion with pain as well as a high failure rate with the need of additional curettage, whereas high satisfaction was observed in women in whom misoprostol treatment resulted in complete evacuation. The individual weighing of the perceived advantages and disadvantages of both treatments generally should be respected after an open counselling, since some women are willing to trade a treatment burden and possible failure of misoprostol for the benefit of a non-invasive management.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Creinin MD, Harwood B, Guido RS, Fox MC and Zhang J (2004) NICHD Management of Early Pregnancy Failure Trial. Endometrial thickness after misoprostol use for early pregnancy failure. Int J Gynaecol Obstet 86, 2226.[CrossRef][ISI][Medline]
de Vries J (1994) Dutch Translation MHLCA [Wallston KA, Wallston BS, DeVellis R, (1978) Development of the Multidimensional Health Locus of Control (MHLC) Scales. Hlth Educn Monogr 6, 160170].
Demetroulis C, Saridogan E, Kunde D and Naftalin AA (2001) A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure. Hum Reprod 16, 365369.
Graziosi GCM, Mol BWJ, Reuwer PJH, Drogtrop A and Bruinse HW (2004) Misoprostol versus curettage in women with early pregnancy failure after initial expectant management: a randomised trial. Hum Reprod 19, 18941899.
Hays W (1998) Statistics. Holt, Rinehart &Winston, New York.
Larsen DL, Attkisson CC and Hargreaves WA (1979) Assessment of client/patient satisfaction: development of a general scale. Eval Program Plann 2, 197207.[CrossRef][Medline]
Lee DT, Cheung LP, Haines CJ, Chan KP and Chung TK (2001) A comparison of the psychologic impact and client satisfaction of surgical treatment with medical treatment of spontaneous abortion: a randomized controlled trial. Am J Obstet Gynecol 185, 953958.[CrossRef][ISI][Medline]
Muffley PE, Stitely ML and Gherman RB (2002) Early intrauterine pregnancy failure: a randomized trial of medical versus surgical treatment. Am J Obstet Gynecol 187, 321325.[CrossRef][ISI][Medline]
Neugebauer R (2003) Depressive symptoms at two months after miscarriage: interpreting study findings from an epidemiological clinical perspective. Depress Anxiety 17, 152161.[CrossRef][ISI][Medline]
Sahin HG, Sahin HA and Kocer M (2001) Randomized outpatient clinical trial of medical evacuation and surgical curettage in incomplete miscarriage. Eur J Contracept Reprod Health Care 6, 141144.[ISI][Medline]
Stewart AL (1988) The medical outcome study short-form general health survey. Med Care 7, 724735.
Thapar AK and Thapar A (1992) Psychological sequelae of miscarriage: a study using the general health questionnaire and the hospital anxiety depression scale. Br J Gen Pract 42, 9496.[ISI][Medline]
van der Ploeg H (2001) Self rating manual. Swets & Zeitlinger, Lisse.
Wood SL and Brain PH (2002) Medical management of missed abortion: a randomized clinical trial. Obstet Gynecol 99, 563566.
Zung W (1965) A self rating depression scale. Arch Gen Psychiat 12, 6370.[ISI][Medline]
Zwinderman AH (1992) Statistical analysis of longitudinal quality of life data with missing measurements. Qual Life Res 1, 219224.[CrossRef][Medline]
Submitted on December 30, 2004; resubmitted on March 6, 2005; accepted on March 14, 2005.
|