Vaginal bleeding is uncommon after TA CVS but is seen in 7% to 10% of patients sampled transcervically. Minimal spotting is a common occurrence and may occur in almost one-third of women sampled by the TC route.17 In most cases, the bleeding is self-limited and the pregnancy outcome is excellent. However, a subchorionic hematoma may be visualized immediately after sampling in up to 4% of TC samples.27 The hematoma usually disappears before the 16th week of pregnancy and is only rarely associated with adverse outcome. Of the more than 15,000 CVS procedures performed in our center, we have never needed to terminate a pregnancy or admit a patient for excessive postprocedural bleeding.
Cases of heavy bleeding and resulting hematoma formation occur from accidental placement of the TC catheter into the vascular decidua basalis underlying the chorion frondosum. In extreme cases, the development of the hematoma can actually be seen on ultrasound. In most of these cases, a gritty feeling indicates penetration into the decidual layer. Careful attention to the feel of the catheter and avoidance of unnecessary manipulation can prevent most of these hemorrhagic episodes and minimize this complication.
Since the initial development of TC CVS, there has been concern that transvaginal passage of an instrument would introduce vaginal flora into the uterus. This possibility was confirmed by cultures that isolated bacteria from up to 30% of catheters used for CVS.28,29, and 30 However, in clinical practice, the incidence of post-CVS chorioamnionitis is low.16,17,31,32 In a recently published US study of more than 2000 cases of TC CVS, infection was suspected as a possible etiology of pregnancy loss in only 0.3% of cases.17 Infection after TA CVS also occurs and has been demonstrated, at least in some cases, to be secondary to bowel flora introduced by inadvertent puncture by the sampling needle.
In our own series of more than 15,000 procedures in which prophylactic antibodies are not used, we have not observed any cases of chorioamnionitis requiring uterine evacuation. Our incidence of periabortion chorioamnionitis was 0.08% for both TC and TA sampling; this rate is about the same as that seen in series of spontaneous abortions that have not been sampled.33,34 At present, because of the clinically low incidence of post-CVS chorioamnionitis, routine pre-CVS vaginal or cervical cultures for any organism other than gonococcus is not indicated.
Early in the development of TC CVS, 2 life-threatening pelvic infections were reported.35,36 Each initially presented with a mild prodrome of maternal myalgias and low-grade fever without localized adnexal or uterine tenderness and subsequently led to maternal sepsis. Both occurred early in the respective center's experience, and in both the same catheter was used for repeat insertions. Since these reports, a practice of using a new sterile catheter for each insertion has been universally adopted, with only exceedingly rare reports of serious infectious complications.
Acute rupture of the membranes, documented by either obvious gross fluid leakage or a decrease in measurable amnionic fluid on ultrasound evaluation, is a very rare complication of CVS.17,37 In our own experience, acute rupture of the membranes has not occurred. Experimental attempts to rupture membranes intentionally with a TC catheter have confirmed that the chorion can withstand significant punishment without perforation.
Gross rupture of the membranes days to weeks after the procedure is acknowledged as a possible post-CVS complication. Delayed rupture can result from either mechanical injury to the chorion at the time of sampling with rupture from exposure of the amnion, or chronic irritation or inflammation from a hematoma on low-grade infection, allowing exposure of the amnion to subsequent damage or infection. One group reported a 0.3% incidence of delayed rupture of the membranes after CVS,32 a rate confirmed by Brambati et al.27
Unexplained mid-trimester oligohydramnios has been suggested as a rare complication of TC CVS and may occur from delayed chorioamnion rupture with slow leakage of amniotic fluid.37 These cases are frequently associated with postprocedure bleeding and an elevated maternal serum α-fetoprotein (MSAFP). Operator experience will markedly reduce the risk of this complication, probably by decreasing hematoma formation with its potential to serve as either a nidus for a smoldering infection or a chemical irritant of the membranes.
An acute rise in MSAFP after CVS has been consistently reported, implying a detectable degree of fetal maternal bleeding.38,39, and 40 The elevation is transient, occurs more frequently after TA CVS, and appears to be dependent on the quantity of tissue aspirated.40 Some studies have also demonstrated a correlation between the degree of elevation and the incidence of pregnancy loss.41 Levels will drop to normal ranges by 16 to 18 weeks, which allows neural tube defect (NTD) serum screening to proceed according to usual prenatal protocols.
In Rh-negative women, the otherwise negligible fetal maternal bleeding that follows CVS accrues special importance because Rh-positive cells in volumes as low as 0.1 mL have been shown to cause Rh sensitization.42 Because all women with even a single pass of a catheter or needle show detectable rises in MSAFP, it seems prudent that all Rh-negative nonsensitized women undergoing CVS receive Rho (D) immunoglobulin subsequent to the procedure.
The potential for a CVS-induced maternal-to-fetal transfusion to worsen already existing Rh immunization has been described, suggesting that sampling sensitized patients represents a contraindication to the procedure.43
Multiple reports from individual centers have demonstrated the safety and low pregnancy loss rates after CVS.8,44,45,46,47,48,49,50, and 51 In experienced centers, the rate of miscarriage from the time of CVS until 28 weeks of gestation is approximately 2% to 3%.19 However, to determine the incidence of procedure-induced pregnancy loss, adjustments for the relatively high background loss at this gestational age must be made.
First-trimester spontaneous abortion in women not undergoing CVS is a common event, occurring in 1 in every 6 clinically recognized pregnancies.52 However, miscarriage rates after ultrasound confirmation of a viable gestation are expected to be less. Simpson et al reported that, when ultrasound confirmation of fetal viability was noted at 8 weeks, 3.2% of 220 women with a mean age of 30 years aborted.53 Christiaens and Stoutenbeek noted a 3.3% fetal loss rate in 274 women with proven fetal viability at 10 weeks.54 Because the majority of women undergoing CVS are older than 35 years and the spontaneous miscarriage rate increases with advancing maternal age, this variable must also be considered. Wilson et al found a total fetal loss rate after proven viability by first-trimester ultrasonography of 1.4% in women younger than 30 years, 2.6% in those between 30 and 34 years old, and 4.3% in women older than 35 years.55 It appears that the best estimate of the background spontaneous miscarriage rate in a population of women similar to those undergoing CVS is approximately 2% to 3%. Although this rate is similar to the postprocedure loss rate in other centers, a randomized clinical trial is necessary to quantify the procedure-induced risk precisely. Unfortunately, no randomized comparison of sampled with unsampled patients is likely; however, comparisons to amniocentesis have been performed.
Because the background loss rate is higher in the firsttrimester than in the second, any comparison of CVS to second-trimester amniocentesis must enroll all patients before the gestational age at which CVS is performed. The total loss rates can then be compared. All losses must be included, whether from a spontaneous miscarriage or an induced termination for abnormal results. This approach eliminates any bias that may occur when comparing procedures performed at significantly different gestational ages, and also takes into account cytogenetically abnormal embryos that miscarry before an amniocentesis, which would be electively terminated after CVS.
The largest demonstrations of data evaluating the relative safety of CVS and amniocentesis come from 3 recent collaborative reports. In 1989, the Canadian Collaborative CVS-Amniocentesis Clinical Trial Group reported its experience with a prospective, randomized trial comparing TC CVS with second-trimester amniocentesis.16 During the study period, patients across Canada were only able to undergo CVS in conjunction with the randomized protocol. There were 7.6% fetal losses (spontaneous abortions, induced abortions, and late losses) in the CVS group and 7.0% in the amniocentesis group. Thus, in desired pregnancies, an excess loss rate of 0.6% for CVS over amniocentesis was obtained; this difference was not statistically significant.
Two months after the publication of the Canadian experience, the first American collaborative report appeared.17 This study was a prospective, although nonrandomized, trial of more than 2200 women who chose either TC CVS or second-trimester amniocentesis. Patients in both groups were recruited in the firsttrimester of pregnancy. As in the Canadian study, advanced maternal age was the primary indication for prenatal testing. When the loss rates were adjusted for slight group differences in maternal and gestational ages at enrollment, an excess pregnancy loss rate of 0.8% referable to CVS over amniocentesis was calculated, which was not statistically significant.
Whereas both North American trials showed no statistical difference in pregnancy loss when CVS was compared with amniocentesis, a prospective, randomized collaborative comparison of more than 3200 pregnancies sponsored by the European MRC Working Party on the Evaluation of CVS demonstrated a 4.6% greater pregnancy loss rate after CVS (95% confidence interval [CI], 1.6% to 7.5%).36 This difference reflected more spontaneous deaths before 28 weeks of gestation (2.9%), more terminations of pregnancy for chromosomal anomalies (1.0%), and more neonatal deaths (0.3%) in the CVS group.
The factors responsible for the discrepant results between the European and North American studies remain uncertain, but it is probable that inadequate operator experience with CVS accounted for a large part of this difference. Whereas the US trial consisted of 7 centers and the Canadian trial 11 centers, the European trial included 31 sampling sites. There were, on average, 325 cases per center in the US study, 106 in the Canadian study, and only 52 in the European trial. Although no significant change in pregnancy loss rate was demonstrated during the course of the European trial, it appears that the learning curve for both TC and TA CVS may exceed 400 or more cases.56,57 Operators having performed fewer than 100 cases may have 2 or 3 times the postprocedure loss rate of operators who have performed more than 1000 procedures.
The consensus of the recent literature indicates that with experienced operators, the procedural complication rates with CVS and amniocentesis is comparable; however, CVS is more difficult to learn.5
There have been similar comparisons between CVS and early amniocentesis, defined as amniocentesis performed before 14 weeks of gestation. In these comparisons of 2 firsttrimester procedures, consideration of gestational age differences is not necessary. Nicolaides et al compared TA CVS with amniocentesis performed between 10 and 13 weeks and gestation.58 In this prospective comparison, the spontaneous loss rate was significantly higher after early amniocentesis (5.3%) than after CVS (2.3%). Also, a significant increase in the incidence of talipes equinovarus was seen after early amniocentesis. In another recent comparison, Sundberg et al randomized patients to either amniocentesis between 11 and 13 weeks or TA CVS between 10 and 12 weeks.3 Although the initial end point of this trial was intended to be pregnancy loss, the trial was stopped early because of an increased risk of talipes equinovarus in the early amniocentesis group. Although the power of the trial to compare fetal loss rates was limited by the incomplete sample, no significant difference was demonstrated. The amniocentesis loss rate, however, was 0.6% higher. Leakage of amniotic fluid after sampling occurred significantly more frequently after amniocentesis. Overall, the higher loss rates, increased risk of fluid leakage, and subsequent club foot deformity with early amniocentesis suggest that CVS is the preferred technique for first-trimester sampling.