Objective
To determine whether a correlation exists between gestational ages of idiopathic recurrent pregnancy loss (iRPL).
Study Design
Cohort of women with iRPL who had an initial loss (qualifying pregnancy [QP]) with precise documentation of gestational age. Outcomes in the immediate next pregnancy (index pregnancy [IP]) were compared between preembryonic (group I), embryonic (group II), or fetal (group III) losses in the QP.
Results
Three hundred thirty-four women met inclusion criteria. In their IP, group I had 41% preembryonic, 28% embryonic, and 10% fetal losses. Group II had 14% preembryonic, 53% embryonic, and 9% fetal losses. Group III had 19% preembryonic, 23% embroyonic, and 29% fetal loses. Correlation coefficient for type of loss among the QPs and IPs was 0.14, P = .009.
Conclusions
Women with iRPL tend to have losses recur in the same gestational age period. Causes for RPL may be gestational age specific and should guide further investigations into causes.
Human reproduction is a remarkable but inefficient process. Maximally fertile couples have only an approximately 30% chance of conception in a given menstrual cycle, and average monthly fecundity is 20%. Successful conception does not guarantee a live birth. Instead, over 30% of conceptions are lost early in gestation. Many of these likely result from problems with implantation or very early conceptus development and may not be clinically apparent. However, 12% to 14% of conceptions result in clinically recognized pregnancy loss. The causes of clinical recognized pregnancy loss also are poorly understood in many cases.
Recurrent pregnancy loss, often defined as greater than 2 or 3 consecutive losses with no more than 1 live birth, occurs in 1-3% of couples, a percentage that is greater than would be expected solely by chance. Purported causes of recurrent pregnancy loss include genetic abnormalities, uterine malformations, antiphospholipid syndrome, hormonal abnormalities, other immunologic disorders, and other causes. However, in 50% or more of cases, no single-cause etiology is found. These women are considered to have idiopathic recurrent pregnancy loss (iRPL). Little progress has been made over the years in regard to causes, treatments, and prognosis for patients with this devastating condition.
It seems to us very likely that causes of pregnancy loss differ during the preembryonic, embryonic, and fetal periods. Furthermore, the timing of pregnancy loss may have prognostic implications for future pregnancies. We hypothesized that that in women with iRPL, losses recur at similar gestational ages. However, precise details regarding gestational age at the time of pregnancy loss are lacking from most published studies of recurrent pregnancy loss (RPL). Our purpose was to determine whether a correlation exists between gestational ages of recurrent losses in a cohort of pregnancies with precise gestational dating in women with iRPL.
Materials and Methods
The study was approved by the University of Utah Institutional Review Board. Study participants were identified through a recurrent miscarriage database that includes patients referred to our practice for evaluation of recurrent pregnancy loss. Uniform data were ascertained regarding prior pregnancies, medical problems, and diagnostic evaluations of either individual or recurrent fetal losses. Testing for recognized causes of pregnancy loss was at the discretion of the primary physician.
Inclusion criteria were as follows: a history of RPL, defined as 2 or more pregnancy losses, and inclusion in the aforementioned database from March 2001 through December 2006, at least 1 unexplained pregnancy loss with precise documentation of gestational age at the time of loss (qualifying pregnancy [QP]) and at least 1 pregnancy subsequent to the QP. The first pregnancy after the QP was termed the index pregnancy (IP). Medical and obstetric histories were abstracted by review of medical records and, in some cases, patient interview. Women with known causes of RPL were not included. IP that resulted in elective terminations or ectopic pregnancies also were excluded from analysis. Patients who had suffered losses after either chorionic villus sampling or amniocentesis were not included.
Pregnancy losses were characterized as precisely as possible with regard to gestational age, using sonographic measurements, evaluation of the delivered fetus, or both. Pregnancies were divided into the following groups: previous pregnancies, QP, IP, and subsequent pregnancies. Precise documentation of gestational age was considered present if a sonogram documented a crown rump length with no fetal cardiac activity or a gestational sac without an embryo or fetal pole. In cases with delivery of a formed fetus, fetal biometric measurements were considered indicative of gestational age.
Patients were divided into 3 groups based on the timing of their first well-characterized pregnancy loss: group I: preembryonic (<6 weeks’ gestation); group II: embryonic (6 through 9 weeks and 6 days); and group III: Fetal (≥10 weeks). Preembryonic pregnancy was defined as sonogram findings including: (1) Mean sac diameter >20 mm with no embryo, (2) mean sac diameter >8 mm without yolk sac, or (3) yolk sac >6 mm with no embryo. Embryonic demise was defined as an embryo with crown-rump length >5 mm, <50 mm, and no cardiac activity. Fetal death was defined as the intrauterine demise of a fetus known to be alive at or beyond 10 completed weeks of gestation documented by (1) detection of fetal heart tones, (2) the ultrasonographic detection of a conceptus with biometric measurements indicating a gestational age at or beyond 10 weeks of gestation, or (3) the delivery of a dead conceptus whose size indicated a gestational age at or beyond 10 weeks’ gestation. Women with losses beyond 16-18 weeks were included in the cohort.
Data were analyzed with SAS version 9.2 (SAS Institute, Inc., Cary, NC). Categorical outcomes were compared with the χ 2 or Fisher’s exact test. Continuous outcomes were measured using Spearman’s correlation coefficients and linear regression models. Data were analyzed using (1) the IP only and (2) all subsequent pregnancies.
Results
Three hundred thirty-four women were identified that met inclusion criteria. One hundred nine women had a preembryonic loss, 131 had an embryonic demise, and 94 had fetal demise at the time of QP. Demographics and patient characteristics at the time of the QP are shown in Table 1 . Groups were similar with regard to age, ethnicity, and medical history.
| Demographic | Group I Anembryonic loss (<6 wk) (n = 109) | Group II Embryonic loss (6.0-10.0 wk) (n = 131) | Group III Fetal loss (>10.0 wk) (n = 94) | P value |
|---|---|---|---|---|
| Age at QP (mean) | 27.3 | 28.5 | 28.0 | .26 |
| Age at IP (mean) | 28.3 | 29.7 | 29.1 | .23 |
| Diabetes, n (%) | 1 (0.9) | 1 (0.8) | 0 | > .99 |
| HTN, n (%) | 2 (1.8) | 0 | 2 (2.1) | .19 |
| Tobacco use, n %) | 4 (3.7) | 5 (3.8) | 1 (1.1) | .47 |
| Thyroid disease, n (%) | 7 (6.4) | 9 (6.9) | 6 (6.4) | > .99 |
| Family history of RSAB, n (%) | 6 (5.5) | 16 (12.4) | 8 (8.6) | .18 |
The Figure illustrates the timing in gestation of all QPs in the cohort. The vast majority of losses occurred before 14 weeks’ gestation. Early fetal deaths (10-14 weeks’ gestation) and preembryonic losses (<6 weeks’ gestation) also were common. Noteworthy, is the striking mode at 4 weeks of gestation, which is generally consistent with previous studies.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
