Many people recommend the routine use of ultrasound in early pregnancy. The differential diagnosis of bleeding in the first trimester includes:
● Intrauterine gestation (normal, normal with a sub-chorionic bleed, early failure)
● Extrauterine gestation (ectopic pregnancy)
Figure 3–13 Normal intrauterine gestation 7 weeks menstrual age.
The patient presented with spotting but went on to a full-term deliv-ery. The fetus can be seen with the amniotic membrane surrounding it and the yolk sac anterior to it.
3 Abnormal Premenopausal Vaginal Bleeding
33
Normal with a Subchorionic Hemorrhage
Subchorionic hemorrhage can be seen in a pregnancy that continues to term, but there is an increased risk of preg-nancy failure depending on the size of the bleed (Fig.
3–14). Not all patients with a subchorionic hemorrhage will present with bleeding. If near the internal os, the sub-chorionic hemorrhage is more likely to be associated with vaginal bleeding than if it is near the fundus and remains concealed.
Sonographically, there may be a small fluid collection beneath the membranes that is the cause of the vaginal bleeding. The collection of blood can look echogenic ini-tially, become echo-free, and may then disappear as the blood is reabsorbed (Fig. 3–15).
This is also discussed later in relation to early preg-nancy failure.
Figure 3–14 Normal intrauterine gestation 7 weeks menstrual age, with a small echogenic subchorionic hemorrhage (arrow). The preg-nancy carried on to term.
Figure 3–15 Subchorionic hemorrhage. Midsagittal scans of a 12.5, 14, and 17.5 week pregnancy. (A) Demonstrates a pos-terior placenta with an echogenic area (arrow) in the lower uterine segment anteriorly. This is a recent subchorionic bleed. (B) The amnion and chorionic membranes are elevated but the space (arrow) is now echo-free. This is liquefied blood.
(C) This scan at 17.5 weeks shows that in the anterior lower uterine segment, the subchorionic bleed is now gone.
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Immunologic Disorders—Antisperm or Anticonception antibodies
● Antiphospholipid antibodies (APAs)
● Anticardiolipin antibodies
The role of APAs and anticardiolipin antibodies is a matter of some debate. In 238 women, Simpson et al16 found that, these antibodies were present before and at 21 days of gestation, the time of implantation. They found no increase in the levels when comparing women who delivered normally with those who had single or recurrent abortions.
● Lupus anticoagulant
● Thyroid-thyroglobulin and microsomal antibodies (TGT)
● Embryotoxic factor (ETA)
● Natural killer cells-systemic CD56 and CD16 cell
● Deficiency in transforming growth factor -2 produc-ing suppressor cells in uterine tissue near the placental attachment site
● Uterine defects that affect implantation—scarring, my-omata,17congenitally small or distorted cavity caused by a uterine septum18
● Unknown
First-Trimester Pregnancy Loss Without Bleeding
Goldstein19studied 232 first-trimester private practice pa-tients with an endovaginal scan at the first visit to deter-mine the incidence of pregnancy loss. All patients had a positive urinary pregnancy test and no history of vaginal bleeding. All patients were followed to delivery or sponta-neous abortion. In the embryonic period (i.e., 70 days from last menstrual period), 27 (11.5%) losses occurred and 4 (1.7%) losses in the fetal period. Specifically, the losses dur-ing the first 10 weeks can be further broken down based on what was visible sonographically by endovaginal scanning (Table 3–3). With each landmark, there was a reduction in Early Failure
Bleeding is also the hallmark of the abnormal pregnancy, occurring in most cases of early pregnancy failure. Approx-imately half of the women who bleed in early pregnancy will ultimately abort. In almost 40% of patients, a failed early pregnancy will be diagnosed by the initial ultrasound examination.12
Bleeding alone has a better prognosis than bleeding with pain and cramps. The pain of abortion may simulate that of labor, being anterior and rhythmic. It may, however, be only an ache or simulate low back pain.
The treatment of non-life threatening bleeding in early pregnancy is mostly expectant. The physical exam will rule out local, more superficial causes. An ultrasound examina-tion will identify the site and size of the gestaexamina-tion and may indicate the likelihood for a successful outcome. In the otherwise uncomplicated gestation with bleeding, bed rest and occasionally intramuscular injections of proges-terone are used. The scientific efficacy for the use of syn-thetic progestational agents is not strong.
The etiology of first-trimester pregnancy loss is still not fully understood. There is a multitude of known and suspected causes. The spontaneous failure rate is ~75% postim-plantation failure rate of 18 to 31%. The higher numbers may reflect the use of a more sensitive pregnancy test to detect a greater number of preclinical losses, which oth-erwise had a following implantation and spontaneous abortion.
Causes of First-Trimester Pregnancy Loss
Fetal (70%)
● Nonrecurring chromosomal abnormalities are the most common cause. X monosomy or trisomy may be seen due to errors at the time of gonadogenesis during meiosis. Triploidy may occur during fertilization, with two sperm entering the egg. Tetraploidy or mosaics will occur during the first division of the zygote.
● Abnormal placental formation.
Maternal (30%)
● Maternal age over 35 years.14
● Paternal age over 35 years.
● Systemic influences—insulin-dependent diabetes, smoking, alcohol consumption.
● Luteal phase defect or corpus luteum failure.15
Table 3–3 First-Trimester Pregnancy Loss in Private Patients without Bleeding19
Fetal period 14 to 20 weeks 2.0
Abbreviations: CRL, Crown rump length.
the loss rate. Once an embryo had achieved a crown-rump length (CRL) of greater than 6 mm or 7 weeks menstrual age (MA), the loss rate until term was between 0 and 3%.
First-Trimester Pregnancy Loss with Bleeding
In the world of the primary care physician, bleeding in early pregnancy is still defined in terms of the amount of bleeding, passage of tissue, size of the uterus, and whether the external cervical os is open. Nonetheless, it is impor-tant for the sonologist to understand the traditional defini-tions and classification. Remember that these designadefini-tions are used only prior to the sonographic evaluation.
Clinical Classification of First-Trimester Bleeding and Potential Pregnancy Loss20
Spontaneous abortion—Termination of a pregnancy prior to the 20th week gestation or 139 days. Spontaneous abortion implies the expulsion of any or all of the products of conception.
Complete abortion—Expulsion of all of the products of conception before the 20th week of gestation.
Incomplete abortion—The expulsion of only some of the products of conception up to the 20th week.
Threatened abortion—Uterine bleeding before the 20th week, with or without uterine contractions, or expul-sion of products of conception and without dilatation of the cervix.
Inevitable abortion—Uterine bleeding before the 20th week of gestation with continuous and progressive cervical dilatation and without expulsion of products of conception.
Missed abortion—The embryo or fetus dies in utero before the 20th week and is retained for 8 weeks or more.
Subclinical spontaneous abortion—The pregnancy is aborted or resorbed before it has been recognized. The incidence is ~16% in the normal fertile population.
Infected abortion—Abortion associated with infection of the genital organs.
Septic abortion—An infected abortion with generalized spread through the maternal circulation.
Studies of Pregnancy Loss with Bleeding
In 1987, Stabile et al12reported on 624 women referred to an emergency gynecological clinic with a provisional diagnosis of threatened abortion. They all had a history of amenor-rhea and vaginal bleeding, with or without pain. No preg-nancy was present in 25% (158/624), with the most com-mon causes of bleeding being follicular/luteal cyst (32) and pelvic inflammatory disease (26). Ectopic pregnancy was diagnosed in 9.6% (60/624). The remaining 406 patients were pregnant and of these, 61.5% (250/406) presented be-tween 7 and 10 weeks. All women underwent a transab-dominal ultrasound study through a full urinary bladder
with a 3.5 MHz transducer. The clinical outcome resulted in 55.9% live births and 44.1% failed pregnancies, a signifi-cantly higher proportion than the 11.5% abortion rate of nonbleeding patients in the Goldstein19study (Table 3–4).
If one discounts the patients who had a subsequent abortion (therapeutic or spontaneous), then 36% (146/406) of patients with a threatened miscarriage had a nonviable pregnancy (i.e., no live fetus) diagnosed at first presenta-tion by transabdominal ultrasound. This study since its publication is 13 years old and does not include studies in-vestigated with the more sensitive endovaginal technique.
Falco et al21prospectively studied a group of 270 patients with transvaginal ultrasound between 5 and 12 weeks ges-tation with first-trimester bleeding. Forty-five percent were excluded, revealing a nonviable pregnancy, a sac without an embryo, or multiple gestation. The exact numbers of each were not recorded. Of the 149 remaining patients with demonstrable fetal cardiac activity, 15% (23/149) patients aborted. They predicted the probability of abortion based on the following abnormal sonographic findings:
● Slow embryonic heart rate (less than 1.2 SD from the mean).
● This varied with CRL from 90 bpm at 10 mm to 120 bpm at 30 mm and was the best criterion. This sign was not very sensitive (0.30), but when present was highly specific (0.93).
● Mean gestational sac diameter minus crown rump length less than 0.5 SD of the mean.
● Small sac size was the next most important finding, al-though it was seldom present (sensitivity of 0.39 and specificity of 0.88). A difference of less than 5 mm was associated with pregnancy failure in 80 to 90% of cases.22 A discrepancy of 5 to 8 mm also had an increased risk.
● Discrepancy between menstrual and sonographic age of 1 week due to slow embryonic growth.
● Subchorionic hematoma was seen in 17% of cases, equally common in continuing and aborted pregnan-cies, but of no value in predicting outcome.
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Table 3–4 Clinical Outcome of 406 Pregnant Patients with Bleeding12
Results Number Percent Ultrasound
Normal pregnancy 227 55.9 Live fetus
Anembryonic pregnancy 67 16.5
Incomplete abortion 41 10.1
Missed abortion 34 8.4
Therapeutic abortion 26 6.4 Live fetus
Spontaneous abortion 6 1.5 Live fetus
Complete abortion 4 1.0
Molar pregnancy 1 0.2
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increased risk of preterm delivery between 34 and 37 weeks (5.6 vs. 11.9%), and increased prelabor rupture of membranes (1.9 vs. 7%).
The rate of spontaneous abortion in the studies of women with and without bleeding is summarized in Table 3–5.
Sonographic Findings of Early Pregnancy Failure
1. Small gestational sac size before 9 weeks; associated with triploidy and trisomy 16.27
2. 3-D sac volume that is smaller than expected.28 3. No embryonic cardiac activity, with a CRL 5 mm.29 4. Embryonic bradycardia relative to CRL.30
There is a 100% loss rate if: (a) the CRL is 5 mm and the rate is 80 bpm, (b) the CRL is 5 to 9 mm and the rate is 100 bpm, or (c) the CRL is 10 to 15 mm and the rate is 110 bpm.
5. Gestational sac larger than 8 mm without a yolk sac.
6. Gestational sac larger than 16 mm without an embryo.
7. Mean sac diameter minus CRL is less than 5 mm (Fig.
3–16).
8. CRL that is smaller than expected.31 9. Poor sac growth.
The sac grows normally at a rate of 1 mm mean sac diameter per day. If the patient is followed for 4 to 7 days and the sac fails to grow appropriately, a failed pregnancy will most likely result.
10.Large yolk sac ( 5.6 mm prior to 10 weeks).
11.Abnormally large or floppy amniotic sac.32
The description of a failed pregnancy based on the ul-trasound examination should be more descriptive than has been customary in the past. I favor the term early preg-nancy failureto describe when there is an intrauterine ges-tational sac but no clearly visible embryo, although there may be a yolk sac and even an amniotic sac present. This term is much more appropriate than the conventional terms of blighted ovum or missed abortion.
If an embryo is present having a CRL 5 mm, but with no demonstrable cardiac activity, then I refer to it as an early embryonic demise. In the second trimester, this would, by definition, be called a fetal demise.
The routine use of ultrasound in early pregnancy has helped clinicians manage cases of bleeding in early Bennett et al23found that the presence of a subchorionic
bleed was associated with a higher incidence of pregnancy failure. In a retrospective study of 516 first-trimester pa-tients with bleeding, a live fetus, and a subchorionic hematoma, they found a loss rate of 18.8% for a large hematoma involving two thirds of the chorionic sac. This was double their overall loss rate of 9.3%. Pandya et al24 supported this association in a screening study, finding a pregnancy failure rate with bleeding of 5.1% with spotting, and 10.5% with heavy bleeding. The risk of spontaneous abortion was increased by 2.3 times when spotting oc-cured, and 4.7 times when there was heavy bleeding.
In a screening study of 17,870 women between 10 and 13 weeks gestation, Pandya et al24found the early preg-nancy failure rate in London, England, to be 2.8%. Of the 501 cases, 313 (62.5%) were missed abortions with a dead embryo visible and 188 (37.5%) were anembryonic with an empty sac. These were patients invited to participate in a study of fetal nuchal fold thickness and included patients with and without bleeding. A transabdominal study was routinely done and if no fetal heart was detected then a transvaginal exam was performed. The risk of sponta-neous abortion, compared with the normal group, was in-creased with vaginal bleeding and maternal age over 40 years (2.48 times). The risk was not significantly affected by previous pregnancy loss or smoking, and decreased with increasing gestational age. The latter association (i.e., gestational age) is understandable if one remembers that there is a high reported incidence (45 to 70%) of chromo-somal abnormalities, most commonly autochromo-somal tri-somies in miscarriages. The lethal forms will abort early in pregnancy, giving a decreased rate of failure later in the first trimester.
Ball et al25found an increased risk of miscarriage (odds ratio 2.8, 95% confidence interval 1.7 to 7.4), stillbirth (4.5, 1.5 to 13.2), abruptio placentae (11.2, 2.7 to 46.4), and preterm labor (2.6, 1.5 to 4.6), when cases were compared with controls without subchorionic hemorrhage or bleed-ing. It is important to remember that bleeding alone in early pregnancy increases the risk of miscarriage.
In a prospective, cohort-controlled study of 214 women presenting with first-trimester bleeding, Johns and Jauni-aux26 found a first-trimester miscarriage rate of 9.3%, an
Table 3–5 Summary of the Rates of Spontaneous Abortion in Women with and without Bleeding
Author Gestational Age (Weeks) Number Indication Abortion Rate (%)
Goldstein (1994)19 5–10 232 Routine 11.5
Pandya et al (1996)24 10–13 17,870 Routine 2.8
Stabile et al (1987)12 5–16 624 Bleeding 45.0
Falco et al (1996)21 5–12 270 Bleeding 51.5
Falco et al (1996)21 5–12 149 Bleeding live fetus 15.0
Pandya et al (1996)24 10–13 17,870 Bleeding 15.6
Johns, Jauniaux (2006)26 7–13 214 Bleeding 9.3
pregnancy, but the pregnancy outcome is difficult to pre-dict accurately and requires careful counseling and timely followup.33Most women will opt for conservative manage-ment of an early pregnancy failure.