Department of Obstetrics and Gynaecology, Miscarriage Clinic, Liverpool Women's Hospital, Crown Street, Liverpool L8 7SS, UK
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: fetal cardiac activity/idiopathic recurrent miscarriage/pregnancy outcome
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In the absence of predicted success rates with idiopathic recurrent miscarriage, the clinician is at a disadvantage in the miscarriage clinic setting, where the most commonly posed question concerns the chance of future pregnancy success. Previous population studies are small, and few have documented sufficient patient numbers to generate confidence with clinical prediction of future pregnancy outcome, in terms of success or failure. The effect of emotional support, supplemented by ultrasound in early pregnancy gives `success rates' of between 70 and 80% (Stray-Pedersen and Stray-Pedersen, 1984; Liddell et al., 1991
; Clifford et al., 1997
). As important as an overall success rate, however, is the significance of each gestational milestone attained in the first trimester, which has not been previously determined.
In this large prospective study, an attempt has been made to identify important gestational milestones for women presenting with idiopathic recurrent miscarriage and used the data analysis to predict future pregnancy success based on gestational age, maternal age and miscarriage history.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Following preconceptual presentation to the clinic, an accurate patient history was taken and investigations performed to exclude known associations of recurrent pregnancy loss, such as antiphospholipid syndrome, oligomenorrhoea (Quemby and Farquharson, 1993; Hasegawa et al., 1996; Drakeley et al., 1998
), cervical weakness and other rarer causes, for example, abnormal parental chromosome karyotype, as previously described (Drakeley et al., 1998
). Patients with identified causes for their pregnancy loss, those who had a history of second trimester loss and those who had completed successful treatment of an abnormal finding were then excluded from the study sample, leaving the `idiopathic' recurrent miscarriage patients. A separate database was then set up for these patients (Li, 1998
) and all results of the investigations performed were recorded including number of previous miscarriages and live births. Further differentiation of the group was made into primary losers (n = 173, those with no previous live births) and secondary losers (n = 152, those with previous live births).
Following early presentation to the clinic in a subsequent pregnancy, all patients followed a standardized clinic protocol including transvaginal ultrasonography using transducers of 7.55 MHz to assess fetal viability on a fortnightly basis until 12 weeks gestation. Thereafter, they were followed up in the Pregnancy Support Antenatal Clinic. The gestation at which cardiac activity was initially seen was recorded on the database along with the outcome of the pregnancy. A successful outcome was regarded as survival beyond 24 weeks. A record was made of the gestational age at which cardiac activity was lost. Ectopic pregnancy and termination of pregnancy in the subsequent pregnancy were excluded from the study sample.
Using the results from the database, a KaplanMeier survival curve was constructed to show time-dependent pregnancy success, in terms of gestational age commencing at 4 weeks amenorrhoea. Logistic regression analysis was subsequently performed, using the model outlined below, to examine the individual impact of age and miscarriage history on achieving a successful pregnancy outcome. The formula for the logistic regression model was:
|
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The mean age of the study sample was 32 years (range 1745 years) and the mean number of previous miscarriages was three (range 210) (Table I).
|
|
The entire group of 222 patients suffered 55 (25%) further miscarriages, 54 in the first trimester and one in the second trimester. Of these 55 miscarriages, six (3% of all pregnancies) occurred following detection of fetal cardiac activity.
Using the KaplanMeier curve (Figure 1), time-dependent survival, in terms of gestational age, was demonstrated. It was clear from this survival curve that the most perilous time for women with a history of idiopathic recurrent miscarriage was between 6 and 8 weeks gestation. Between these gestations, 78% of the pregnancy losses occurred, 89% of which occurred without the detection of fetal cardiac activity (embryo loss).
Fetal cardiac activity had been identified in 90% of the pregnancies by 8 weeks, rising to 98% by 10 weeks. Consequently, by 8 weeks gestation, if a fetal heart beat had been identified, the chances of a successful outcome in a subsequent pregnancy were 98%, climbing to 99.4% at 10 weeks gestation (Table II).
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
The concept of gestational milestones has been used to predict pregnancy success at 6, 8 and 10 weeks gestation. For the entire population there was a 22% loss rate at 6 weeks gestation, which dramatically fell to 2% at 8 weeks and subsequently at 10 weeks gestation fell to 0.6% of the remaining population (Table I). The conclusion would be that the most perilous time of gestation for women with idiopathic recurrent miscarriage is between 6 and 8 weeks.
Maternal age
Increasing maternal age reduces the chance of a pregnancy success. This has been confirmed in 201 women undergoing fertility treatment by ovulation induction (Smith and Buyalos, 1996). These authors clearly showed an increasing rate of pregnancy loss from 2.1% at less than 30 years to 20% in women over 40 years of age. Furthermore, the impact of age is profound within large infertility populations undergoing in-vitro fertilization (IVF) (Templeton et al., 1996
). This study concluded that maternal age is singularly the most important determinant in predicting pregnancy success in an IVF population.
The profound impact of maternal age on pregnancy outcome is similarly demonstrated in the present study. For example, a woman aged 20 years with two previous miscarriages has a 92% [confidence interval (CI) 8698] chance of success in a subsequent pregnancy. This, however, falls dramatically to 60% (CI 4179) in a woman with a similar loss history who is aged 45 years (Table II). Although the confidence intervals for the success prediction are wide at the extreme ends of the age spectrum, there is little doubt that maternal age has a significant impact on future success in the recurrent miscarriage population.
Pregnancy support
The effect of the provision of tender loving care and emotional support on loss rates in recurrent miscarriage populations has been previously evaluated. The first large population study, utilizing tender loving care and emotional support in the first trimester, showed an 80% success rate in patients with idiopathic recurrent miscarriage (Stray-Pedersen and Stray-Pedersen, 1983). This study, however, identified 85 out of 195 couples as having `idiopathic recurrent miscarriage' and the population was quasi-randomized, based purely upon geographical location. A separate study, in the absence of tender loving care, showed an 80% success rate, when studied in a smaller population (n = 24) with similar characteristics (Vlaanderen et al., 1987). A more recent study reported an 86% success rate with tender loving care (n = 33), as opposed to only 33% in the absence of emotional support (n = 9), in an unrandomized population (Liddell et al., 1991). Both these recent studies are restricted by small numbers, in contrast to the present study of 222 consecutive pregnancies from which a 75% success rate has been obtained with the provision of tender loving care and ultrasound in early pregnancy.
Patient empowerment
Women with a history of idiopathic recurrent miscarriage, understandably exhibit a marked stress reaction following early diagnosis of a subsequent pregnancy. Ultrasound reassurance and emotional support in a specialized Miscarriage Clinic may address this problem and go some way to alleviating this stress. The present large population study, as well as determining success rates for the group as a whole, has also identified important gestational milestones for success prediction. These milestones can empower patients to gain increasing reassurance of a potential successful pregnancy outcome, as advancing gestation is reached. Clinicians can also gain confidence from this data to predict the future chances of pregnancy success in women with a history of idiopathic recurring miscarriage.
![]() |
Acknowledgments |
---|
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Christiaens, G.C. and Stoutenbeek, P.H. (1984) Spontaneous abortion in proven intact pregnancies. Lancet, 2, 571.
Clifford, K., Rai, R. and Regan, L. (1997) Future pregnancy outcome in unexplained recurrent first trimester miscarriage. Hum. Reprod., 12, 387389.[Abstract]
Drakeley, A.J, Quenby, S. and Farquharson, R.G. (1998) Mid-trimester loss appraisal of a screening protocol. Hum. Reprod., 13, 19751980.[Abstract]
Everett, C. (1997) Incidence and outcome of bleeding before the 20th week of pregnancy: prospective study from general practice. Br. Med. J., 315, 3234.
Gilmore, D.H. and McNay, M.B. (1985) Spontaneous fetal loss rate in early pregnancy. Lancet, i, 107.
Goldstein, S.R. (1994) Embryonic death in early pregnancy: a new look at the first trimester. Obstet. Gynaecol., 84, 294297.[Abstract]
Hasegawa, I., Takakuwa, K. and Tanaka, K. (1996) The role of oligomenorrhoea and fetal chromosomal abnormalities in spontaneous abortion. Hum. Reprod., 11, 23042305.[Abstract]
Hill, L.M., Guzick, D., Fries, J. and Hixon, J. (1991) Fetal loss rate after ultrasonically documented cardiac activity between 6 and 14 weeks menstrual age. J. Clin. Ultrasound, 19, 221223.[ISI][Medline]
Li, T.C. (1998) Guides for practitioners. Recurrent miscarriage: the principles of management. Hum. Reprod., 13, 478482.[ISI][Medline]
Liddell, H.S., Pattison, N.S. and Zanderigo, A. (1991) Recurrent miscarriage: outcome after supportive care in early pregnancy. Aust. N. Z. J. Obstet. Gynaecol., 31, 320322.[ISI][Medline]
Lind, T. and McFadyen, I.R. (1986) Human pregnancy failure. Lancet, i, 91.
Liu, D.T.Y., Jeavons, B., Preston, C. et al. (1987) A prospective study of spontaneous miscarriage in ultrasonically normal pregnancies and relevance to chorionic villus sampling. Prenat. Diagn., 7, 223.[ISI][Medline]
Lyndon, M., Hill, M.D., Guzick, D. et al. (1991) Fetal loss rates after ultrasonically documented cardiac activity between 6 and 14 weeks menstrual age. J. Clin. Ultrasound, 19, 221223.[ISI][Medline]
Mackenzie, W.E., Holmes, D.S. and Newton, J.R. (1988) Spontaneous abortion rates in ultrasonographically viable pregnancies. Obstet. Gynaecol., 71, 8183.[Abstract]
Opsahl, M.S. and Petit, D.C. (1993) First trimester sonographic characteristics of patients with recurrent spontaneous abortion. J. Ultrasound Med., 12, 507510.[Abstract]
Qasim, S.M., Sachdev, R., Trias, A. et al. (1997). The predictive value of first-trimester embryonic heart rates in infertility patients. Obstet. Gynecol., 6, 934936.
Quenby, S. and Farquharson, R.G. (1993) Predicting recurring miscarriage what is important? Obstet. Gynaecol., 82, 132138.[Abstract]
Smith, K.E. and Buyalos, R.P. (1996) The profound impact of patient age on pregnancy outcome after early detection of fetal cardiac activity. Fertil. Steril., 65, 3540.[ISI][Medline]
Stirrat, G.M. (1990) Recurrent miscarriage; definition and epidemiology. Lancet, 336, 673675.[ISI][Medline]
Stray-Pedersen, B. and Stray-Pedersen, S. (1984) Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am. J. Obstet. Gynecol., 148, 140146.[ISI][Medline]
Templeton, A., Morris, J.K. and Parslow, W. (1996) Factors that affect outcome of in-vitro fertilisation treatment. Lancet, 348, 14021406.[ISI][Medline]
Vlaanderen, W. and Treffers, P.E. (1987) Prognosis of subsequent pregnancies after recurrent spontaneous abortion in first trimester. Br. Med. J., 295, 9293.[ISI][Medline]
Wilson, R.D., Kendrick, V., Wittmann, B.K. et al. (1986) Spontaneous abortion and pregnancy outcome after normal first-trimester ultrasound examination. Obstet. Gynaecol., 67, 352.[Abstract]
Submitted on February 15, 1999; accepted on July 28, 1999.