Department of Obstetrics and Gynaecology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
1 To whom correspondence should be addressed. E-mail: tamwh{at}cuhk.edu.hk
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Abstract |
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Key words: medical evacuation/miscarriage/reproductive outcome
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Introduction |
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Women have also expressed high acceptance and satisfaction towards conservative management without substantial adverse psychological impact (Sahin et al., 2001; Lee et al., 2001
; Wieringa-de Waard et al., 2002b
; Ngoc et al., 2004
). Medical evacuation may also offer economic benefits from the reduction in the number of operations (Hughes et al., 1996
; Graziosi et al., 2004
). Although most of the recent studies have been focused on the efficacy of various regimens and routes of administration of medical treatment (Pang et al., 2001
; Gronlund et al., 2002
; Tang et al., 2003
; Phupong et al., 2004
), little has been reported on the long-term fertility and pregnancy outcomes following these conservative treatment alternatives.
Infertility following miscarriage could be the consequence of tubal damage from infection or intrauterine adhesion either from surgical treatment or secondary to infection. Although concerns had been raised about the infective risks of non-surgical management (Jurkovic, 1998), published data suggested that medical evacuation resulted in similar or reduced rate of pelvic infection following miscarriage (Chipchase and James, 1997
). Hysteroscopic examinations at 6 months post-abortion revealed a low rate of intrauterine adhesions in subjects managed with ERPC but none in those managed with medical evacuation (Tam et al., 2002
).
Hence, a non-surgical approach to the management of miscarriage appears to offer the advantage of minimizing unnecessary surgical interventions while maintaining low rates of morbidity from miscarriage. Fertility outcome following conservative management of miscarriage has only been addressed by a few studies of relatively small sample sizes and short duration of follow-up (Ben Baruch et al., 1991; Blohm et al., 1997
; Graziosi et al., 2005
). As the subsequent long-term fertility is an important concern in counselling women regarding the choice of management for miscarriage, more data in this area are needed.
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Materials and methods |
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The medical evacuation misoprostol protocol used to manage miscarriage has been previously described (Chung et al., 1999). Women who were diagnosed with incomplete miscarriage [area of echogenic shadows on transvaginal ultrasound scan (TVS) transverse plane >5 cm2, or that of sagittal plane >6 cm2] or missed abortion (intact gestational sac on TVS) were randomized to either medical evacuation with misoprostol or immediate ERPC. In the medical evacuation arm, patients were given misoprostol 400 µg orally every 4 h to a total dose of 1200 µg. TVS was repeated on the following day. Those with an empty uterus (area of echogenic shadows on TVS transverse and sagittal planes
5 and
6 cm2 respectively) after misoprostol treatment were discharged from hospital while those with incomplete evacuation underwent ERPC. Out of the 635 women entered into the randomization, 604 (95.1%) received the assigned treatment. The reasons for deviation from the intention to treat were explained in the previous publication.
From the original cohort, 423 could be contacted but four women declined interview with a response rate of 69.4%. The baseline characteristics of the cohorts available and not available for follow-up were similar in the number of previous live births, termination of pregnancies and miscarriages except that the cohorts available were older (31 versus 33 years; P = 0.01). Four patients in the medical evacuation group and six patients in the surgical evacuation group were excluded from analysis because of previous miscarriage, being molar pregnancy, known history of infertility prior to the previous miscarriage, or sterilization during the last miscarriage (Figure 1). A total of 261 women among the responders (61.7%) reported that they had attempted to become pregnant after treatment of the index miscarriages.
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The baseline characteristics, previous reproductive history, contraceptive methods and natural conception rate were compared using MannWhitney U-test, 2 and Fishers exact test where appropriate by using SPSS 11.0 (SPSS Inc., Chicago, IL, USA). The cumulative pregnancy rates over time were calculated for both groups by using KaplanMeier survival analysis and compared using log-rank test (GraphPad PrismTM 4.0; GraphPad Software, Inc. San Diego, USA). The outcome measures were dichotomous as either pregnant or not pregnant achieved by natural conception over the defined period. The starting point for the calculations was the date of the treatment if the couple did not use any contraception after the miscarriage or the date of cessation of contraceptive methods if the couple practised contraception. The endpoint was the date of the first positive pregnancy or the date 8 months before the delivery of a term pregnancy. For those women who failed to become pregnant by natural conception, the endpoint was the date of the telephone interview. The time-to-pregnancy was calculated from the time the couple attempted to conceive till the endpoint. If pregnancy was obtained by any aid of infertility treatment, the woman was censored from the analysis at the date the treatment began.
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Results |
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The natural conception rates were the same in both groups following the previous treatments for miscarriage (97.7%; P = 0.99). There was no significant difference in the subsequent live birth rate in the immediate pregnancy following previous treatment between the two groups (85.2 versus 88.2%; P = 0.72). The median time-to-pregnancy (interquartile ranges) was 8 months in both medical and surgical groups respectively (not significantly different; P = 0.97) (Table I). One woman in each arm suffered infertility and required ovulation induction to achieve pregnancy.
The cumulative pregnancy rate by natural conception for each group is shown in Figure 2. Women treated by medical evacuation had a fertility rate similar to those treated by standard surgical evacuation (P = 0.92, log-rank test). The cumulative pregnancy rates in both groups at first and second years were 60 and
80%. With the surgical evacuation as the reference, the hazard ratio for medical evacuation is 0.98 (95% CI 0.761.29). A post hoc power analysis shows that the sample size can detect 13 and 12% difference in the pregnancy rate at the first and second years respectively with 80% power at a 0.05 significance level.
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Discussion |
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In a previous publication, we examined the occurrence of intrauterine adhesion following the two treatment protocols as a surrogate indicator to reflect the likelihood of long-term fertility problems (Tam et al., 2002). The prevalence of de novo adhesions was much lower than previously reported. This would imply that adverse effects on fecundity in both conservative and surgical evacuations, if any, are minimal. Previous studies which compared fertility after either conservative or surgical management were limited by small sample size. One study included only 14 women who indicated they wanted to become pregnant in one treatment group (Blohm et al., 1997
). Another was a follow-up of a non-randomized observational study in which the entry criterion was empty uterus on ultrasound scan, hence not relevant to those with incomplete miscarriage or missed abortion managed with a conservative approach (Ben Baruch et al., 1991
). Furthermore, the latter only had 35 cases in the conservative arm. Furthermore, the proportion who attempted to conceive was not clear. The small size in both studies is an obvious limitation in detecting any real difference in the subsequent fertility rate between the two treatment approaches. Recently, Graziosi et al. (2005)
reported a cohort of 126 subjects and showed a similar fertility rate after either conservative or surgical treatment for previous miscarriages.
Our present data showed that the median time interval time-to-pregnancy was 8 months in both medically and surgically treated cohorts. The live birth rates and miscarriage rates were also similar between the two groups. However, the time-to-pregnancy seems slightly longer than expected for a normal population with a cumulative natural conception rate after 1 year of 60% in both groups. This could be explained by several reasons.
Firstly, the cohort does not represent a normal population and may have lower fecundity. More than 30% of the women had two or more miscarriages and 30% also had a previous termination of pregnancy. In a recent study which evaluate previous aberrant reproductive outcome and fecundity, time-to-pregnancy doubled after one previous miscarriage compared to that after a previous live birth, and the cumulative pregnancy rate at 12 months was reduced from 86 to 76% after a miscarriage (Hassan and Killick, 2005). This suggests a potential reduction of fecundity after one previous miscarriage irrespective of the treatment received.
Any reproductive data based on recall may be subjected to error and the number of miscarriages may have been under-reported (Wilcox and Horney, 1984; Harlow and Linet, 1989
; Kristensen and Irgens, 2000
). Since our study groups consisted of an a priori group of women with a high rate of miscarriage, we would expect a higher subsequent miscarriage rate as suggested in the literature (Ben Baruch et al., 1991
). Surprisingly, we found a lower rate of miscarriage. The time-to-pregnancy could have been overestimated if some women failed to recall an immediate miscarriage, remembering only a live birth after the previous treatment. Recall bias on the contraceptive history may also introduce error to the calculation of time-to-pregnancy. Time of cessation of contraception may not have been recalled accurately and methods such as coitus interruptus and abstinence are usually poorly documented.
Lastly, only 70% of the cohort were available for the follow-up and the non-responders could have had different fertility and reproductive outcomes. Nonetheless, the previous reproductive history appears similar between the responders and non-responders. Despite the response rate and potential recall bias in the present study, there does not appear to be an adverse impact on fecundity following a non-surgical approach to management compared to surgical evacuation. These findings offer useful information for counselling on the safety and pregnancy rate following medical evacuation of miscarriage.
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Acknowledgements |
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References |
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Submitted on May 26, 2005; resubmitted on July 6, 2005; accepted on July 15, 2005.
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