Biology and Medicine
Editor-in-Chief: Eytan R. Barnea MD, FACOG
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EARLY
PREGNANCY: Biology and Medicine Editor-in-Chief: Eytan R. Barnea MD, FACOG |
October 2000
Volume IV, Number 4
ISSN: 1537-6583
Pages: 253-260
Frequency Of Etiological Factors And Cost Effectiveness Of The Work Up For Patients With History Of Recurrent Pregnancy Loss
Shawky Z. A. Badawy, MD, Edith M. Westpfal, MD
Department of Obstetrics/Gynecology, SUNY Health Science Center, Syracuse, New York
Correspondence: Shawky Z.A. Badawy, MD, Department of Obstetrics/Gynecology, 736 Irving Ave., Syracuse, NY 13210, Phone: (315) 470-7905, Fax: (315) 470-7999
Keywords: recurrent miscarriage, recurrent fetal wastage
Abstract
Objective
To assess the frequency of the etiological factors during the evaluation of
patients with recurrent abortions. The cost effectiveness of the most frequent positive
findings will be assessed.
Study Design
This is a retrospective study in which 97 patient charts were evaluated and
only 90 charts were included in this study. The diagnostic studies for every patient
including hysterosalpingogram, endometrial biopsy, cervical cultures for Chlamydia and
ureaplasma, and chromosomal karyotyping for the couple were assessed. The cost analysis
was based on the CPT coding for each test.
Results
The frequency of the tests with highest positive findings were
hysterosalpingogram, endometrial biopsy, cervical cultures, and immunologic studies.
Chromosomal karyotyping has a low positive yield in evaluation of these patients.
Conclusion
In evaluating patients with recurrent miscarriages, treating physicians
should take into consideration the tests which have a high positive yield as a first step.
Chromosomal karyotyping should be evaluated in specific situations.
Introduction
Recurrent pregnancy loss is a devastating problem for both the patient and the treating physician. Patients with such problems always spend variable periods of time grieving their loss, and they may blame themselves or their partners for this problem. They present to their treating physician hoping to find an answer to this problem and a solution to treat the etiological factors in order to achieve a successful pregnancy. However, the problem is also very frustrating to the treating physician since the majority of these patients will have normal evaluation for the various factors. Proper, intensive counseling and group support is needed to help these women to ease their grief and maintain a pregnancy. (1)
Recurrent pregnancy loss is defined as two consecutive pregnancy losses. This is the definition which is used clinically by most gynecologists before initiating the evaluation protocol. It is also realized that waiting for three pregnancy losses before the evaluation, imposes too much psychological stress on the patients since the risk of losing a third pregnancy is estimated to be about 35%.(2)
The incidence of two consecutive miscarriages is about 5%, and three or more miscarriages is 1% for all women. The chance for subsequent pregnancy loss was considered in the past to be at 22-84%.(3-4) More recent data suggests that the chance for recurrent pregnancy loss ranges between 20-35% depending on the number of previous pregnancy losses.(5)
Gynecologists, as part of the health care program system resort to various tests which will give the patient the required standard of care. However, the treating physician should consider the cost effectiveness of such tests, since insurance carriers nowadays require preauthorization for testing.
The present study demonstrates the incidence of the various factors leading to recurrent miscarriages and the cost effectiveness in our practice at Upstate New York.
Materials and Methods
This is a retrospective study of patients who were diagnosed with history of
two or more recurrent pregnancy losses for the period between January 1992 and January
1998. Ninety-seven patient charts were reviewed; however, seven charts were excluded
because the patients did not undergo the evaluation for recurrent pregnancy loss at our
institution.
The present study attempts to evaluate the frequency of the various etiological factors in patients with recurrent fetal wastage. In addition, the study will compare the cost of the evaluation for the whole protocol and also for the more frequent positive tests.
The study protocol includes history of physical activity, nutrition, smoking, alcohol intake, and the gestation age at which the pregnancy was previously lost. A physical examination was completed including blood pressure, weight, and height of the patient. Patients were evaluated for evidence of any endocrinopathies in the form of hirsutism, obesity, and any evidence of hypo or hyperthyroidism. A pelvic examination was completed including cervical cultures for Chlamydia, ureaplasma, and pap smears. The uterine contour was assessed for congenital anomalies and/or the presence of fibroids of the uterus. The adnexae were also assessed for any abnormalities.
The following tests were ordered: T4, TSH, serum prolactin level, hysterosalpingogram, endometrial biopsy during the luteal phase of the cycle, anticardiolipin antibodies, lupus anticoagulant, ANA antibodies, and chromosomal karyotyping in the peripheral blood for the patient and her partner.
All these patients had a health profile previously, which showed normal fasting blood sugar and normal electrolytes. A cost analysis was based on CPT coding for each test.
Results
The frequency of etiologic factors for recurrent pregnancy loss is outlined in Table I. It is clear from the data that 39% of the patients had abnormal hysterosalpingograms including uterine septum (31.9%), submucous polyps or submucous myomas (43.4%) and intrauterine synechiae (25%). Luteal phase defect were present in 38.6% of the patients. Positive cervical cultures for Chlamydia or ureaplasma was present in 31% of the patients. Chromosomal karyotyping was abnormal in 13.2% of the patients including three women with balanced translocations, two women with mosaicism, two women with inversions, and one male with Klinefelter's. Immunologic studies were positive in 23.6% of the patients. It is interesting to note that idiopathic recurrent pregnancy loss was present in 24.7% of our patients. Comorbidities were present in 43.8% of our patients (Table I).
The cost of all these tests per patient in the Syracuse area was about $2,094 (Table II). The frequency of the tests with highest positive findings were lysterosalpingogram, endometrial biopsy, cervical cultures, and immunologic studies. The cost for undergoing these tests will be $1,197 per patient (Table III).
Discussion
Protocols for evaluation of patients with recurrent fetal wastage are derived from scientific data from various studies in the literature. In addition, patients are also exposed to news media that may affect their decision in requesting some experimental testing. It is our duty, therefore, to present to every patient the scientific data as applicable to her particular situation. It is equally important that we spend enough time in counseling and education so that patients realize the significance of every test and its importance in diagnosing and managing recurrent miscarriages. The anger and frustration of the patients should be well appreciated and we believe that the treating physician should wait until patients overcome the stage of grief before any evaluation is started.
The present study certainly showed that the majority of patients with recurrent pregnancy loss have positive findings following evaluation by our protocol. Only 24.7% did not have any etiological factors according to this protocol. This is, of course, less than what has been previously reported in the literature. Furthermore, we found that 43.8% of the patients have multiple factors. This is important for the treating physician to realize that doing a single test is not going to be helpful even if the result is positive and a cohort of several significant testing has to be done to discover those cormorbidities.
In this study the yield of positive results was very low in the endocrine testing in the form of thyroid and prolactin studies. It was also relatively low with chromosomal karyotyping. This does not necessarily reflect negatively on the importance of these tests. However, they may be ordered in special situations where there is family history or objective data in the history, suggestive of chromosomal abnormalities and/or thyroid disease. Certainly, elderly women may require these tests since such abnormalities may be higher than in a younger group of women.
The cost analysis for running the whole protocol will be $2,094. The cost analysis for running the significant tests with high frequency of positive results including hysterosalpingogram, endometrial biopsy, cervical cultures, and immunologic studies will be $1,197 only.
Indeed, the use of hysterosalpingogram, endometrial biopsy for evaluation of the luteal phase, cervical cultures, and immunologic studies will be satisfactory as a first line of studies. This will give us a high percentage of yield for positive values in patients with recurrent fetal wastage. The treatment of the abnormal findings from these tests will lead to a high salvage rate with regards to continuation of the pregnancy and prevention of fetal loss. Abdominal and hysteroscopic metroplasty improved the live birth rate to 75-80 percent.(6-7) Luteal phase defect has been treated with induction of ovulation and/or luteal phase support using progesterone therapy with high successful results.(8) Ureaplasma and Chlamydia infection of the cervix and endometrium has been suspected for causing recurrent miscarriages due to endometritis. Higher antibody titer to Chlamydia trachomatis was found in women with recurrent miscarriages that in those without history of miscarriages. Treatment of these infections leads to improvement in pregnancy salvage.(1,9,10) The role of antiphospholipid syndrome in recurrent abortions is well established. Treatment with baby aspirin and heparin have been shown to reduce fetal loss significantly.(1,12,13)
At the present time, the use of various specific tests for evaluation of recurrent miscarriages with high yield of positive results may have contributed to the reduction of idiopathic recurrent miscarriage rates. Indeed, the incidence of idiopathic cases in our series is only 24.7% as compared to previously published reports of 35-44%.(14) This group of patients often needs intensive counseling because their probability of achieving successful pregnancy is 60-70%. These patients may consider exploring the new technologies available including the use of lymphocyte immunization or intravenous gamma globulins.(15) These methods will need further testing to improve their cost effectiveness.
In conclusion, the protocols for evaluation of recurrent pregnancy loss includes many tests, but some have higher yields of positive findings than others. Furthermore, the protocols are evolving to include some tissue compatibility studies in idiopathic cases. Treating physicians always are directed by evidence based medicine to perform tests and give the proper care. We believe that this is the perfect approach. However, this sometimes may be in conflict with cost and insurance carrier policies. We always have to keep our options open to be able to help this group of patients that are affected with such serious problems. Treating physicians have always to act as consultants and take the time to discuss with the patients and their insurance carrier the need for the intensive testing based on the published data.
For personal use. Only reproduce with permission from SIEP.
References
Table I
Frequency of Etiologic Factors of Recurrent Pregnancy Loss TEST
No Patients % POSITIVE
Hysterosalpingogram 84 33(39%)
Endometrial biopsy 83 32(38.6%)
Cervical Cultures 71 22(31%)
Karyotype 76 10(13.2%)
Immnologic
Antinuclear antibody 42 4(9.5%)
Lupus anticoagulant 43 4(9.3%)
Anticardiolipin antibody 83 4(4.8%)
Thyroid 89 6(6.75%)
Prolactin 80 3(3.8%)
Idiopathic 89 22(24.7%)
Comorbidities 89 39(43.8%)
Table II
Cost Analysis
STUDIES COST
Hysterosalpingogram $568
Endometrial biopsy $312
Cervical cultures $163
Karyotype (couple) $752
Immunologic $154
Antinuclear antibody $ 42
Lupus anticoagulant $ 60
Anticardiolipin antibody $ 52
Thyroid $145
Prolactin $ 40
Total $2094
Table III
Cost Analysis for Most Frequent Etiologic Factors
TEST COST
Hysterosalpingogram $568
Endometrial biopsy $312
Cervical cultures $163
Immunologic studies $154
Total $1197
