objectives - also-scandinavia

Chapter A

First Trimester Pregnancy ComplicationsMark Deutchman, MD • Amy Tanner Tubay, MD • David Turok, MD

Published August 2010

ObjectivesAfter completing this chapter, participants will be able to:

• Discuss the value of hCG sonographic discriminatory criteria in diagnosing first trimester

pregnancy complications.

• Describe the process, diagnosis and management of miscarriage.

• Describe the process, diagnosis and management of ectopic pregnancy.

• Describe the process, diagnosis and management of gestational trophoblastic disease.

• Describe the spectrum of psychological reactions to early pregnancy loss.

• Describe the techniques of suction curettage for the treatment of incomplete miscarriage.

IntroductionComplications of the first trimester of pregnancy are common. About fifteen percent of clinically

recognized pregnancies miscarry spontaneously and estimates of losses prior to clinical recognition

reach nearly 50 percent.1 In addition to miscarriage, vaginal bleeding may be associated with ecto-

pic pregnancy, trophoblastic disease, cervical bleeding from causes unrelated to pregnancy or may

occur in pregnancies that proceed otherwise uncomplicated.

Normal First Trimester Pregnancy Progress and Discriminatory CriteriaClinically, pregnancy is dated from the first day of the last normal menstrual period (LMP), an

observable event, rather from than the conception date. Conception is approximately two weeks

later. All gestational landmarks in this chapter are based on menstrual dating; embryology textbooks

commonly use conception dating which is two weeks less.

The placenta produces human chorionic gonoadotropin (hCG) after implantation. Implantation

occurs at around 23 menstrual days, which is about eight days after conception. Commonly avail-

able urine pregnancy tests can detect the beta subunit of hCG at levels of 50 to 100 mIU/ml IRP

(International Reference Preparation) and some can detect hCG at levels as low as 20 mIU/ml.

Serum tests can detect hCG as low as 5 mIU/ml. While it is therefore technically possible to detect

pregnancy prior to a missed period, the majority of over the counter home pregnancy tests will not

be positive until the first week after a missed menstrual period.2 Quantitative serum hCG levels

should double every two to three days during weeks four to eight in normal early pregnancy. Falling

levels, or those that plateau are strong evidence of impending poor outcome but do not distinguish

between spontaneous abortion and ectopic pregnancy.3,4,5 Slide 6 demonstrates hCG patterns in normal first trimester pregnancy versus miscarriage and ectopic pregnancy.

A single serum progesterone level has been shown to be effective in predicting early pregnancy

location when ultrasound findings are inconclusive.6,7 With this method a progesterone level of less

than five nanogram/ml is more likely to be associated with a poor pregnancy outcome (spontane-

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— Chapter A: First Trimester Pregnancy Complications — 1

2 — — Chapter A: First Trimester Pregnancy Complications

ous abortion or ectopic pregnancy) while a progesterone level of greater than 25 nanogram/ml is

strongly associated with a living intrauterine pregnancy. However, this method is rarely employed

as the use of serial quantitative hCG and transvaginal ultrasound have proven to be the most cost

effective strategy for diagnosing ectopic pregnancy.8

The gestational sac first becomes visible sonographically during the fifth menstrual week as a 2 to 5

mm sonolucent area surrounded by an echogenic ring of chorionic villi. This early gestational sac is

visible only using a high frequency transducer (5 MHz or greater) and the transvaginal scan route. A

small sonolucent fluid collection, or pseudosac, may also be present in cases of ectopic pregnancy,

so additional features of a normal gestational sac can be sought including the “intradecidual sign”

indicating that the gestational sac is embedded in the endometrium and not within the endometrial

stripe. The yolk sac appears during transvaginal scanning during the sixth menstrual week and pro-

vides clear evidence of an intrauterine pregnancy. By the end of the sixth menstrual week, the “fetal

pole” 2 mm to 8 mm in length with embryonic cardiac activity becomes visible during transvaginal

scanning. All these sonographic landmarks are visible with transabdominal scanning about one

week later than with transvaginal scanning.9

Discriminatory criteria based on clinical, hCG and sonographic findings are closely correlated and

are displayed in Table 110,11 Ultrasonography is so helpful that, when it is readily available, many

clinicians use it as a primary tool in the evaluating first trimester complications, leaving serum hCG

and/or progesterone testing as a secondary tool to use only if sonographic findings are equivocal.

The greatest diagnostic yield is obtained when first trimester ultrasonography is performed in com-

bination with knowledge of the patient’s history, physical examination and any relevant laboratory

tests that have already been performed. Routine ultrasound in early pregnancy appears to enable

better gestational age assessment, earlier detection of multifetal pregnancies and earlier detection

of multifetal pregnancies, however the benefits for other substantive outcomes are less clear.12

Table 1. Early Pregnancy Discriminatory Findings*

Menstrual Age Embryologic Event Laboratory and Transvaginal Sonographic Discriminatory Findings

Three to four weeks Implantation Site Decidual thickening

Four weeks Trophoblast Peritrophoblastic flow on color flow Doppler

Four to five weeks Gestational SacMust be present if bhCG > 1500 to 2000 mlU/mL (varies with

sonographer experience and ultrasound quality)

Five to six weeks Yolk Sac Must be present if gestational sac mean diameter > 10 mm

Five to six weeks Embryo Seen when gestational sac mean diameter is > 18 mm

Five to six weeks Cardiac Activity Must be present if embryonic crown-rump length > 5 mm

*Adapted from Reference #10.

Once the embryo is visible sonographically, first trimester menstrual age is calculated from crown-

rump length using parameters such as those shown in Table 2. Between eight and 13 weeks, ges-

tational age can be approximated using the simple formula: Menstrual age (weeks) = crown-rump

length (CRL) in centimeters (cm) plus 6.5, or this alternate formula: Menstrual age (days) = crown-

rump length in millimeters (mm) plus 42.

slides 8-11

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Table 2. Crown-rump Length and Menstrual Age

Crown-rump length Menstrual age Crown-rump length Menstrual age

0.2 cm 5.7 weeks 3.0 cm 9.9 weeks









MISCARRIAGE Table 3 defines the many terms that are commonly applied to early pregnancy loss.13,14

Table 3. Terms Applied to Early Pregnancy Loss*

Embryonic Demise — an embryo > 5 mm without cardiac activity. (Replaces the unclear term “missed abortion.”)

Anembryonic Pregnancy — presence of a gestational sac > 18 mm without evidence of embryonic tissues (yolk sac or embryo). This term is preferred to the older and less accurate phrase “blighted ovum.”

Spontaneous Abortion — spontaneous loss of a pregnancy prior to 20 weeks gestation. May be further described as:• Incomplete — occurs when some but not all of the products of conception have passed• Complete — the complete passage of all products of conception• Septic — Incomplete abortion associated with ascending infectino of the endometrium,

parametruim, adnexa, or peritoneum• Inevitable — bleeding in the presence of a dilated cervix, indicating that passage of the

conceptus is unavoidable• Missed — The fetus or embryo has been dead for several weeks but no tissue has been

passed. The cervix is closed. These patients often present with no growth in uterine size or no fetal heart tones being heard.

Threatened Abortion — bleeding before 20 weeks in the presence of an embryo with cardiac activity and closed cervix.

Subchorionic Hemorrhage — Ultrasonographic finding of blood between the chorion and uterine wall, usually seen in the setting of vaginal bleeding.

Recurrent Pregnancy Loss — more than two consecutive pregnancy losses. The phrase “habitual aborter” ahs also been used in this setting but is no longer appropriate.

Ectopic Pregnancy — pregnancy outside the uterine cavity, most commonly in the fallopian tube but may occur in the brad ligament, ovary, cervix or welsewhere inthe abdomen.

Heterotopic Pregnancy — simultaneous intrauterine and ectopic pregnancy. Risk factors include ovulation induction, in vitro fertilization and gamete intra-fallopian transfer.

Gestational Trophoblastic Disease, or Hydatidiform Mole — Complete mole: placental proliferation in the absence of a fetus. Most have a 46 XX chromosomal composition, all derived from paternal source. Partial mole: molar placenta occurring together with a fetus. Most are genetically triploid (69 XXX)

Vanishing Twin — A multifetal pregnancy is identified and one or more fetuses later disappear. More com-monly seen now that early ultrasound scanning is common. It this occurs early in pregnancy, the embryo is often reabsorbed, later occurrence results in a compressed or mummified fetus or amorphous material.

*Adapted from References 13 and 14.

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MISCARRIAGE: PATHOPHYSIOLOGY, CLINICAL COURSE AND DIAGNOSISThe cause of spontaneous abortion is rarely determined in clinical practice, but it is known that

about half are due to major genetic abnormalities, usually trisomy, triploidy, or monosomy.15

Environmental factors linked to spontaneous abortion are shown in Table 4.

Table 4. Environmental Factors Linked to Spontaneous Abortion

Uterine anomalies

Leiomyomata

Incompetent cervix

Tobacco, alcohol or cocaine

Progesterone deficiency due to luteal phase defect

Irradiation

Maternal diethylstilbestrol (DES) exposure

Advanced maternal age

Infections

Occupational chemcial exposure

Spontaneous abortion may present clinically in several different ways. Most commonly, vaginal

bleeding and cramping are present, but occasionally, regression of pregnancy symptoms or lack of

Doppler-detected fetal heart tones by 10 to 12 weeks are the first clinical signs in the setting of anem-

bryonic pregnancy or embryonic demise.

Clinical examination should include palpation of the abdomen and pelvis. The size and position of

the uterus, the location of any tenderness, the presence of rebound tenderness and the presence of

masses should be noted. Adnexal tenderness and any masses should heighten concern for ectopic

pregnancy, although a normal corpus luteum cyst may also be the cause.

If the patient’s last menses was at least nine to ten weeks ago, consider listening for the fetal heart-

beat during the bimanual pelvic exam while elevating the uterus with the examining hand.

The speculum examination will reveal non-uterine causes of bleeding, the degree of cervical dilation

and, if present, tissue being passed. The quantity of blood in the vault and the source of bleeding

(from the os vs. other sites) should be noted. If an intact gestational sac, an embryo, or the char-

acteristic fronds of chorionic villi are seen, miscarriage is proven and ectopic pregnancy is virtually

ruled out except in the rare case of simultaneous intrauterine and ectopic pregnancy (heterotopic

pregnancy). To look for chorionic villi, rinse and float the tissue with saline. Low magnification,

backlighting and “teasing” the tissue may help. Passed tissue should be submitted for pathological

examination which is definitive in questionable cases. Slide 19 shows this finding.

If tissue is seen at the cervical os, miscarriage is inevitable. A ring forceps may be used to gently

remove it. More aggressive attempts to remove partially expelled tissue should be preceded by

discussion with the patient, informed consent and administration of analgesia or sedation.

When the diagnosis is not clear by clinical findings, transvaginal scanning is essential for accurate

diagnosis.

slides 15-19


There are two ultrasonographic findings diagnostic of early pregnancy failure.14 The first is the pres-

ence of a gestational sac with a mean sac diameter of 20 mm or greater without an embryo. This

is diagnostic of an anembryonic pregnancy (Slide 20). The second finding is that of an embryo

five mm or greater in crown-rump length without cardiac activity, diagnosing an embryonic demise.

If there is any doubt about the sonographic findings, close follow-up and re-examination in four to

seven days is reasonable if the patient is stable. Both the gestational sac and the embryo if pres-

ent should each grow at the rate of approximately 1 mm/day, thus allowing for appreciable interval

change in that time period. When ultrasound reveals a heartbeat in a patient who is bleeding, the

probability of miscarriage is between 2.1 percent for women under 35 years of age to 16.1 percent in

women over 35 years of age.16

Complete, spontaneous miscarriage may result in an empty uterus with a bright “endometrial stripe”

indicating the uterine walls have collapsed back against each other and that the miscarriage is com-

plete. When the patient has a history of passing tissue or clots, this finding can help determine if

the miscarriage is complete. Echogenic material within the endometrial cavity commonly creates an

endometrial stripe > 15 mm following medical treatment of early pregnancy failure.17

Septic abortion should be assumed when the patient is febrile or has excessive uterine or adnexal

tenderness, or signs of peritonitis. A previous history of attempted therapeutic abortion or illegal

abortion that may have left tissue behind or perforated the uterus should be sought, an extremely

rare event where abortion services are legal and safe.

In subchorionic hemorrhage, a gestational sac and embryo will be present but sonography will

reveal a hematoma between the chorion and uterine wall. When subchorionic hemorrhage is seen

by ultrasound, the likelihood for miscarriage averages about ten percent, even when a heartbeat is

detected, and varies by maternal age, size of the hematoma and gestational age.18 Therefore the

patient should be warned to expect bleeding.

The quantity of bleeding only predicts pregnancy loss when it is heavy. A prospective analysis of

4,510 women who were followed in the early first trimester showed that 1,204 (27 percent) had some

bleeding or spotting. There was no increase in risk of miscarriage in early pregnancy when there

was spotting or light bleeding. However risk of miscarriage increased significantly in the eight per-

cent of women who reported heavy bleeding. This was the only group to have an increased risk of

miscarriage (Adjusted OR 2.84, 95% CI 1.82-4.43).19

MISCARRIAGE: MANAGEMENTIf ultrasound reveals an intrauterine pregnancy with cardiac motion, the patient may be followed with

cautious optimism and an explanation that there are no known interventions to prevent miscarriage.

When physical examination reveals incomplete miscarriage, the patient must choose between

expectant, medical or surgical management. The majority of first trimester miscarriages occur com-

pletely and spontaneously without intervention. Although surgical intervention in the form of sharp

or suction dilatation and curettage have been used traditionally and liberally, expectant manage-

ment and medical treatment are valid options.20,21,22 Women who are experiencing excessive bleed-

ing, pain, or have infection benefit from medical or surgical intervention.20,21 In an observational

study 22 expectant management led to spontaneous completion of 91 percent of cases of incom-

plete miscarriage, 76 percent of missed abortions and 66 percent of anembryonic pregnancies

slides 20, 21

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within 14 days of diagnosis. Women who have not completed the miscarriage for a long period of

time may prefer medical or surgical intervention. Her emotional state and personal preferences are

important in choosing the course of action.

Clinical trials comparing expectant management with misoprostol and misoprostol with surgical

treatment conclude:23,24,25

• In incomplete miscarriage, both expectant and medical treatments with misoprostol are

highly successful.

• In missed abortion, medical treatment with misoprostol and surgical treatment are more

effective than expectant treatment.

• Typical misoprostol dosages are 600 micrograms orally or 600 to 800 micrograms vaginally

• Women treated with misoprostol have more bleeding but less pain than those treated

surgically.

• Women treated expectantly have more outpatient visits than those treated with misoprostol.

• Surgery is associated with more trauma and infectious complications than misoprostol

treatment.

• Misoprostol has fewer gastrointestinal side effects when given vaginally than when given

orally.

As a result of trials on medical management of miscarriage, a change to less surgical management

has been suggested, even though use of misoprostol for this purpose is not approved by the Food

and Drug Administration.26

There is no evidence supporting the use of prophylactic antibiotics in early pregnancy failure,27

although there is such evidence for induced abortion. When misoprostol is used for medical abor-

tion, the incidence of infectious complications is reduced by administering the drug by the buccal

route and by administering doxycycline 100 mg twice daily for seven days.28 It is unclear whether it

is the use of antibiotics or the change in the route of misoprostol administration that resulted in the

lowered incidence of infection. It is also not clear whether this is also true when misoprostol is used

to treat early pregnancy loss. It is also reasonable for a woman to change treatment course and mix

the three treatment options. Women commonly choose a period of expectant management followed

by medical therapy with misoprostol if they no longer desire to wait. This could also be followed by

dilation and curettage if medical therapy is not successful.

After a miscarriage it is customary to recommend a brief period of contraception before attempting

another pregnancy. However, this practice is not supported in the literature. A prospective study

found no statistically significant difference of recurrent miscarriage in women who had interpreg-

nancy intervals < 6 months versus those who had longer intervals.29 For patients desiring long-term

contraception, an intrauterine device placed immediately after spontaneous or induced first trimes-

ter abortion is safe and effective.30

slides 23-26


ECTOPIC PREGNANCY: PATHOPHYSIOLOGY AND RISK FACTORSEctopic pregnancy is usually located in the fallopian tube but rarely may occur in the broad

ligament, ovary, cervix at the site of a prior hysterotomy or elsewhere in the abdomen. Ectopic

pregnancy can result in impairment or loss of fertility and, due to internal hemorrhage, remains

the second most common cause of maternal mortality. Early diagnosis is the key to preventing

morbidity and mortality and preserving fertility. All health care providers who care for childbearing

age women should have an active working knowledge of ectopic pregnancy, and should have a

high index of suspicion in any woman who presents in early pregnancy with bleeding and/or pain.

Risk factors are shown in Table 5, but many ectopics occur in women without risk factors.

Table 5. Risk Factors for Ectopic Pregnancy

History of tubal surgery, including tubal ligation and/or reanastomosis of the tubes after tubal ligation

History of tubal infection including pelvic inflammatory disease

Contraception with progestin only pills or intrauterine devicesHistory of in utero exposure to diethylstilbesterol

History of pervious ectopic pregnancy

ECTOPIC PREGNANCY: SIGNS, SYMPTOMS AND DIAGNOSISPain and vaginal bleeding are the hallmark symptoms of ectopic pregnancy. Pain is almost univer-

sal; it is generally lower abdominal and unilateral. Bleeding is also very common following a short

period of amenorrhea. Physical exam may reveal a tender adnexal mass, often mentioned in texts,

but noted clinically only 20 percent of the time. Furthermore, it may easily be confused with a tender

corpus luteum of a normal intrauterine pregnancy. Finally signs and symptoms of hemoperitoneum

and shock can occur, including a distended, silent, “doughy” abdomen, shoulder pain, bulging cul-

de-sac into the posterior fornix of the vagina, and hypotension.

Initially, serum hCG rises, but then usually plateaus or falls. Transvaginal ultrasound scanning is a

key diagnostic tool and can rapidly make these diagnoses:

1. Ectopic is ruled out by the presence of an intrauterine pregnancy with the exception of rare

heterotopic pregnancy

2. Ectopic is proven when a gestational sac and an embryo with a heart beat is seen outside of

the uterus

3. Ectopic is highly likely if ANY adnexal mass distinct from the corpus luteum or a significant

amount of free pelvic fluid is seen.31

When ultrasound is not definitive, correlation of serum hCG levels is important. If the hCG is above

the “discriminatory zone” of 1500 to 2000 mIU/ml IRP, a gestational sac should be visible on trans-

vaginal ultrasound.4 The discriminatory zone varies by ultrasound machine and sonographer. If

an intrauterine gestational sac is not visible by the time the hCG is at, or above, this threshold, the

pregnancy has a high likelihood of being ectopic. When serum hCG is less than 1500 mIU/ml, and

ultrasound findings are unclear serial quantitative hCG levels in combination with follow-up imaging

are most useful. Repeat serum hCG should be drawn in 48 hours. Based on a study that followed

287 women presenting in early pregnancy with pain or bleeding, the minimum rise necessary for a

viable pregnancy over this time period is 53 percent.32

slides 27, 28

slides 29-32

slides 33-37


In some cases of ectopic pregnancy, a small fluid collection within the uterus can be mistaken for

a true gestational sac. However, this pseudogestational sac lacks a surrounding echogenic ring of

chorionic villi, a yolk sac or fetal pole. An unruptured corpus luteum cyst or may be mistaken for an

ectopic gestational sac, and a ruptured corpus luteum cyst may produce free pelvic fluid suggest-

ing ruptured ectopic pregnancy. Culdocentesis can be very helpful in differentiating the thin, pink

fluid of a ruptured ovarian cyst which can be managed expectantly from the frank hemorrhage due

to ruptured ectopic pregnancy, but improved use of ultrasound and highly sensitive hCG decreases

the need for this procedure. The presence of ANY cul-de-sac fluid indicates ectopic pregnancy until

proven otherwise. Slides 33, 34 and 36 show sonographic images of extrauterine mass, pseudosac and free pelvic fluid.

When hCG levels are not rising normally and ultrasound cannot confirm pregnancy location, a

dilation and curretage (D&C) or manual vacuum aspiration may yield chorionic villi or a gestational

sac 38 percent of the time.33 When this happens a failed intrauterine pregnancy is diagnosed and

treatment for an ectopic pregnancy avoided. When suspicion for ectopic pregnancy is high but

cannot be confirmed with noninvasive testing, laparoscopy can both confirm the diagnosis and

accomplish treatment.

ECTOPIC PREGNANCY: MANAGEMENT With early diagnosis the management of ectopic pregnancy has firmly moved into the outpatient

realm. Current treatment options favor medical and laparoscopic management34 with expectant

management reserved for cases with a declining quantitative hCG < 1,00035 and open surgical man-

agement limited to cases of tubal rupture and hemoperitoneum. Surgical management via

laparoscopy or open laparotomy can involve complete removal of the fallopian tube (salpingectomy)

or efforts to remove the ectopic pregnancy and conserve the tube (salpingostomy). Ectopic preg-

nancies located in the tubal cornua, interstitial area or uterine cervix are exceedingly dangerous and

difficult to treat. Table 6 shows indications for surgical management.

Table 6. Indications for Surgical Management of Ectopic Pregnancy

Unstable vital signs or signs of hemoperitoneum

Uncertain diagnosis

Advanced ectopic pregnancy (high hCG, large mass, cardiac activity)

Unreliable follow-up

Any contraindication to observation or methotrexate

Expectant or medical treatment are options in hemodynamically stable women who are carefully

selected and informed according to the criteria in Tables 7 and 8.36,37,38 Human chorionic gonado-

tropin level is the best predictor of successful treatment with methotrexate. A systematic review of

several studies showed that failures with single dose methotrexate occurred 3.7 percent of the time

when hCG levels were below 5,000 mIU/ml vs. 14.3 percent when higher than this cut-off. Thus,

methotrexate use is used only in special circumstances when hCG levels exceed 5,000 mIU/ml.39

slides 38-42


Table 7. Criteria for Expectant Management Include:35,36,37,38

Minimal pain or bleeding

Patient reliable for follow-up

No evidence for tubal rupture

Starting hCG level less than 1000 mlU/ml and falling

Ectopic or adnexal mass less than three centimeters, or not detected

No embryonic heartbeat

Table 8. Criteria for Medical Management of Ectopic Pregnancy With Methotrexate35,36,37,38

Stable vital signs and low level of symptomatology

No medical contraindication for methotrexate therapy (normal liver enzymes, complete blood count and platelet count)

Unruptured ectopic pregnancy

Absence of embryonic cardiac activity

Ectopic mass four centimeters or less

Starting hCG levels less than 5000 to 10,000 mlU/ml

Expectant management is used most often when the actual location of the pregnancy cannot be

determined. Medical management with methotrexate, a folic acid antagonist, is appropriate for

properly selected patients and has been shown in randomized trials to be safe and effective; it also

can be less costly and result in equal or better subsequent fertility than conservative surgical treat-

ment.34,40,41,42 As with expectant treatment, patient selection and close follow-up are key to safety

and success. Single dosage intramuscular regimens are commonly calculated at one mg/kg or 50

mg/m2. Protocols for single and multiple dose regimens are shown in Table 9.43 Serum hCG testing

is performed on the fourth and seventh post-treatment days and then followed weekly until the level

reaches 5 mIU/ml, which may take three to four weeks. The hCG initially rises slightly, but should fall

15 percent between days four and seven; if not, the dosage should be repeated or surgical therapy

performed. The methotrexate dosage should be repeated no more than once before surgical con-

sultation is obtained. Because some patients managed expectantly or with methotrexate will eventu-

ally require surgery, prompt consultation is essential for the non-surgeon.


Table 9. Single and Multiple Dose Methotrexate Regimens for Treatment of Ectopic Pregnancy

Supplement to: Barnhart KT. Ectopic Pregnancy. N Engl J Med 2009;361:379-87.

Table 9. Treament Protocols for Ectopic Pregnancy Using Methotrexate (MTX).

Treament Single Dose (46) Two-Dose (47) Multi-dose (48)

Pretreatment, rule out spontaneous abortion

hCG, creatinine, liver function, CBC w/diff



Day #1 Check hCG value, Administer first dose of MTX 50 mg/m2 IM

Check hCG value, Administer first dose of MTX 50 mg/m2 IM

Check hCG value, Administer first dose of MTX 1 mg/kg IM Followed by Leucovorin 0.1 mg/kg IM on Day 2 Check hCG on day 2

Day #4 Check hCG value Check hCG value, Administer second dose of MTX 50 mg/m2 IM

Administer second dose of MTX (day 3) and Leucovorin (day 4) on and respectively. Check hCG on day 4

Day #7 Check hCG value for 15 % decrease between days 4 and 7.

If > 15 % fall, check hCG weekly until not detectable in serum.

If < 15 % fall, administer second dose MTX, 50 mg/m2 IM

Check hCG value for 15 % decrease between days 4 and 7.

If > 15 % fall, check hCG weekly until not detect-able in serum.

If < 15 % fall, administer third dose MTX, 50 mg/m2 IM

Continue administering doses of MTX and Leucovorin (Ie course 3 day 5 and 6 and course 4 day 7 and 8) until hCG values have declined by 15 %. Do not exceed 4 courses

If > 15 % decline, check hCG weekly until not detectable in serum.

Day #11

Check hCG value for 15 % decrease between days 7 and 11.

If > 15 % decline, check hCG weekly until not detectable in serum.

If < 15 % fall, administer fourth dose MTX, 50 mg/m2 IM

Weekly surveillance

If follow-up hCG value plateau or rise, consider surgical intervention or repeat dose of MTX as additional therapy.

If follow-up hCG value plateau or rise, consider surgical intervention or repeat dose of MTX as additional therapy.

If follow-up hCG value plateau or rise, consider surgi-cal intervention or repeat dose of MTX as additional therapy.

Copyright permission obtained from the following Source: Copyright, Massachusetts Medical Society, all rights reserved.


GESTATIONAL TROPHOBLASTIC DISEASE: PATHOPHYSIOLOGY AND RISK FACTORS SLIDESGestational trophoblastic disease, or molar disease is an occasional cause of first trimester bleed-

ing in the U.S. (1:1000 to 1:1500) but is more common in Southeast Asia.

Complete mole consists of placental proliferation in the absence of a fetus. Risk factors include

extremes of age and previous molar pregnancy. The placental villi are swollen and often resemble

bunches of grapes. Most complete moles have a 46 XX chromosomal composition, all derived from

paternal sources Mole recurrence may progress to metastatic choriocarcinoma. Partial mole is a

molar placenta occurring together with a fetus, which is usually non-viable. Genetic testing usually

reveals triploidy (69 XXY). Partial mole is less common than a complete mole, and carries a lower

risk of recurrence.

Gestational Trophoblastic Disease: Signs, Symptoms and DiagnosisThe signs and symptoms of gestational trophoblastic disease are shown in Table 10.

Table 10. Signs and Symptoms of Trophoblastic Disease

Uterus larger than expected for gestational age

Absent fetal heart beat

Higher than expected hCG levels

Hyperemesis, pregnancy-induced hypertension at an early gestational age, and/or thyrotoxicosis

Ovarian enlargement, caused by theca-lutein cysts resulting from ovarian hyperstimulation by the high hCG levels

Vaginal bleeding in the first or early second trimester, which is often dark, and may cause anemia

Grape-like vesicles are passed in cases that progress into the second trimester

In cases of complete mole, ultrasound diagnosis is suggestive when there are multiple vesicular

spaces within the uterus and there is no fetus. Enlarged cystic ovaries are common. While this diag-

nosis is usually quite straight forward in the second trimester it can be very difficult to make in the

first trimester. Especially in the case of a partial mole that has an embryo.

GESTATIONAL TROPHOBLASTIC DISEASE: TREATMENT Prompt evacuation of the uterus is the primary treatment. After evacuation of a complete mole, all

patients should have serial monitoring of hCG for six months to one year with contraception.44 If the

hCG plateaus or rises, then recurrence must be assumed, investigated and treated with chemotherapy

(methotrexate). Because of the relative rarity of the disease and the many possible complications, con-

sultation is recommended. Theca-lutein ovarian cysts require no treatment and will resolve after evacu-

ation of the molar tissue. About 20 percent of women with a complete mole will experience recurrence

in the form of mole that invades the myometrium or becomes aggressively metastatic.

slides 43-46


GRIEF AND PSYCHOLOGICAL MANAGEMENT OF EARLYPREGNANCY LOSS SLIDES Miscarriage represents a major loss to the pregnant woman and her family. The grief reaction that

often follows is similar in intensity to that experienced after other major losses, though women

experience and describe it in varied ways.45 Although healing will occur, the time to recovery also

varies. The feelings of loss tend to be strongest in the first six months after the event,46 but they can

be persistent and pervasive enough to cause long-term symptoms or even affect the patient’s next

pregnancy.47 Women at risk for a stronger grief reaction include those who experienced a missed

abortion, those with loss at a later gestational age, those with a longer time to conception of their

next pregnancy, and those with a critical self-perception.47,48 Partners also experience grief with

pregnancy loss. Because men are often a primary social support for patients and attend up to 20

percent of post-loss visits,49 it is important for the healthcare provider to include them in the care

plan. Available evidence suggests that although the vast majority of women desire support from

their health care provider, many don’t receive the quantity or quality of support they desire.45 The

types of interventions that are most effective in managing psychologic symptoms are still uncer-

tain,50 but the following approaches may be practical ways to mitigate the normal grief that follows

early pregnancy loss.51

Acknowledge and attempt to dispel guilt. Many women believe that some action on their part caused

or contributed to the miscarriage. This guilt may revolve around sexual activity, food, minor trauma,

physical activity or emotional stress. Women whose losses can be ascribed to a definite cause

have lower levels of anxiety and grief.52,53 Therefore, evaluation of available tissue for chromosomal

anomalies is recommended when possible. Even when a definitive cause cannot be ascertained,

reassurance that the patient did nothing to cause the loss is appropriate. This reassurance may need

to be repeated several times. Women should be counseled that genetic or developmental errors

probably occurred early in the pregnancy, and there was no possibility of this pregnancy progressing

to produce a live baby. The post-loss follow-up visit is not the time to focus on modifiable risk factors

that may have contributed to the loss (ie, alcohol or tobacco use). Addressing these issues prior to

future pregnancies is certainly indicated, but is better done after the acute trauma of loss fades. The

patient’s religious belief system may be called on during this counseling.

Acknowledge and legitimize grief. Allowing patients to discuss their emotions surrounding their loss

may be the most important aspect of psychologic care. One study suggests that women who had a

medical follow-up visit at which they were not provided an opportunity to discuss their feelings actu-

ally had more anxiety and depression than those who had no follow-up at all.45 Patients and their

partners should be allowed to cry or feel sad. Minimizing their feelings will isolate them and decrease

the provider’s credibility. Legitimize their feelings by confirming that miscarriage is the death of a baby.

Comments such as “you can try again” or “at least it happened early” are inappropriate. Simple mea-

sures that validate grief should not be underestimated. Listening to the patient, holding her hand, or

telling her how sad you feel for her can help her through this traumatic period. The patient should be

seen within one to two weeks in the office, or called on the phone a few days after the miscarriage.

Reassure about the future. Grief will fade with time. Most patients have an excellent chance of a

subsequent normal pregnancy. With fewer than three miscarriages, the risk of miscarriage in future

pregnancies is no greater than usual. It is important to explain that the next pregnancy will not need

to be managed differently because of the miscarriage. This is an excellent time to encourage the

initiation of a prenatal vitamin.

slides 47,48


Counsel the patient how to tell family and friends of the miscarriage. If family members and friends

knew about the pregnancy, a designated person may inform them of the loss. This allows them to

express their sympathy and provide emotional support, and may avoid embarrassing encounters

in which others assume the pregnancy is progressing uneventfully. If the pregnancy were a secret,

then family and friends may puzzle over any external signs of grief or distress. A decision must

be made whether to tell them. Informing other children in the family may also be difficult, however

families often find comfort in allowing children to share in the grieving and remembering process.54

Parents should be encouraged to discuss the loss in honest and developmentally appropriate ways,

just as they would the death of any other family member.

Warn patients of the anniversary phenomenon. A recurrence of grief feelings on their due date or

the anniversary of the miscarriage may occur. This might also develop at the birth of a friend’s baby

or during their own subsequent pregnancy.47 Posttraumatic stress disorder should be considered

in women experiencing prolonged grieving, anxiety, or other symptoms that affect their general or

reproductive functioning.

Include the partner in your psychological care. Partners often feel the pain of loss and should be

included in counseling and decisions. Men’s reactions to pregnancy loss are more strongly influ-

enced by the status of the marital relationship than are women’s.47 Offering couples counseling and

including fathers in the healing process may speed resolution for both partners.55

Assess level of grief and adjust counseling accordingly. Many women are ambivalent or distressed

by the pregnancy and may experience very mixed feelings or profound relief at the loss. A history

of previous abortion, failed birth control, or rape may further complicate the emotional response.

Allowing the patient to express her emotions in a supportive and non-judgmental atmosphere is

always an appropriate intervention.

RH PROPHYLAXIS AND FUTURE CONCEPTION AFTER PREGNANCY LOSSSeveral follow-up issues must be addressed after any type of pregnancy loss. Rh negative women

who miscarry during the first trimester should receive 50 mcg of anti D immune globulin.56

Contraception should be discussed and started immediately, as all methods are equally safe

immediately following spontaneous abortion or ectopic pregnancy. There is no good evidence sug-

gesting an ideal interpregnancy interval.57 Folic acid supplementation prior to future conception

attempts substantially reduces the risk of neural tube defects.58

SUMMARYFirst trimester pregnancy complications are common and the differential diagnosis includes life-

threatening conditions such as ectopic pregnancy. Knowledge and application of discriminatory

criteria can significantly aid in distinguishing normal early pregnancy from miscarriage and ectopic

pregnancy. While surgical treatment is the mainstay of ectopic pregnancy treatment, medical and

expectant treatments are possible in properly selected cases. In incomplete miscarriage, nonsurgi-

cal treatments have a high likelihood of success but depend on diagnosis; in embryonic demise

or anembryonic pregnancy, misoprostol or surgical treatment are considerably more effective than

expectant treatment. Because there is a lack of clear superiority of expectant versus surgical man-

agement of miscarriage, the woman’s preference should play a dominant role in decision making.59

slide 49

slides 50, 51


When the choice is made to treat early pregnancy failure by other than expectant means, vaginal

misoprostol is highly efficacious, safe and well-accepted by women, with fewer gastrointestinal

side-effects than the oral route. Evidence does not support the use of antibiotics in all women with

incomplete abortion. After any type of first trimester pregnancy loss, Rh negative women should

receive 50mcg of anti D immune globulin. Acknowledgement of grief, empathy and reassurance are

useful techniques in counseling women after miscarriage. Slide 51 shows an algorithm for the diag-

nostic approach to the patient with a positive pregnancy test and pain or bleeding.

OPTIONAL SECTIONSurgical Management of Miscarriage: (Dilation and Curettage and Manual Vacuum Aspiration)The majority of first trimester miscarriages occur completely and spontaneously without interven-

tion, and when intervention is selected, medical management is highly effective. Uterine aspiration

by electric suction or manual vacuum aspiration may be indicated when:

1. Heavy bleeding is present (greater than a pad an hour).

2. Patient is clinically stable (no bleeding or cramping), but pregnancy loss is demonstrated con-

clusively and the patient prefers intervention to expectant management to await for spontane-

ous completion.

3. Ectopic pregnancy needs to be ruled out. In certain situations a clinical distinction cannot be

made between an ectopic and an intrauterine pregnancy. If tissue from a D&C contains chori-

onic villi, the pregnancy was intrauterine. Very rarely, an intrauterine and an ectopic pregnancy

(heterotopic pregnancy) may coexist, creating a confusing and dangerous clinical situation.

Contraindications to Uterine Aspiration 1. Medical contraindications are rare but include active pelvic infection and coagulopathy.

2. Pregnancy loss is not proven to the patient’s satisfaction, the physician’s satisfaction, or both.

3. The patient prefers to await spontaneous completion for any reason (religious beliefs, cost,

desire to avoid surgical procedures, etc.).

Uterine aspiration is not appropriate if the spontaneous abortion appears to be complete by the

following criteria:

• The uterus is small and firm.

• Scant or no bleeding is occurring.

• Tissue has been passed and is available for inspection and appears complete.

• The patient is reliable in follow-up.

• Ultrasound examination (preferably transvaginal) shows an empty uterus.

slides 52, 53

slide 53

slide 54

slide 55


How to Perform a Uterine Aspiration (Suction Dilation and Curettage) Under Local Anesthesia 1. Place an intravenous (IV) line if patient is bleeding heavily or if IV medications are to be used.

2. A hematocrit or hemoglobin and an Rh test should be obtained. A white blood count, pro-

thrombin time, partial thromboplastin time, fibrin split products, and blood type and screen

may be obtained depending on clinical circumstances (e.g. heavy bleeding, missed abortion).

3. Sedation and analgesia should be administered. Two to five mg of IV midazolam (VersedR)

and, 50 to 100 mcg of IV FentanylR are commonly used. Alternatively, 25 to 50 mg of meperi-

dine (Demerol) and/or five to 10 mg diazepam (Valium) may be used. In many situations, the

patient’s partner or another support person may sit with her during the procedure.

4. The size and position of the uterus should be identified by bimanual exam. If the fetal mea-

surements and uterine size are greater than 14 weeks in size, then a dilation and extraction

procedure is indicated which requires advanced training beyond that required for first trimes-

ter aspiration. If a procedure is required beyond 14 weeks consider adding 20 units of oxytocin

to intravenous fluids.

5. The cervix should be exposed with a speculum. A medium Graves speculum usually suffices.

The cervix and posterior fornix are cleansed with an antiseptic solution. The anterior lip of the

cervix is then grasped with a single toothed tenaculum.

6. A paracervical block can be achieved with 10 cc of two percent chloroprocaine (NesacaineR)

or 20 cc of 1 % lidocaine (XylocaineR) via a 20 gauge spinal needle. One fourth of the amount

of the block is administered at 3:00, 5:00, 7:00, and 9:00 or one half the amount of the block

at 4:00 and 8:00 where the cervix meets the vagina. A superficial wheal is raised and the

syringe is aspirated before injecting to avoid intravascular injection. Several variants of the

paracervical block exist, and all are equally satisfactory.

7. If the cervix is closed, or insufficiently dilated to easily admit the required suction curette, it can

be progressively dilated using cervical dilators. Dilation should occur to the number of mm that

is equivalent to the estimated gestatinal age in weeks or one mm less ( e.g, dilate to 9 or 10 mm

to aspirate a ten week missed abortion) Control is indicated for this portion of the procedure,

as dilators and uterine sounds cause the largest number of uterine perforations. If the patient is

clinically stable, overnight dilation with laminaria is an option. Another means of dilation that has

had success, but not FDA approved, is the oral administration of misoprostol (CytotecR) 600

ucg or vaginal administration of 400 ucg two to four hours before the procedure.

8. The uterus is carefully sounded to determine the axis of the cervix and uterine cavity to guide

further instrumentation. If the os is open, a ring forceps or blunt curette can be used as a

sound and any loose tissue encountered can be removed.

9. The suction curette should be equivalent to the size of the uterus in weeks (e.g. a # 10 curette

for a 10 weeks’ sized uterus) is appropriate. A curved curette is used if the uterus is anteflexed

or retroflexed. A straight curette may be used if the uterus is midposition. The suction curette

is inserted along the previously determined axis of the uterus, until slight resistance is felt,

while exerting slight traction on the tenaculum to stabilize the cervix and straighten out the

cervico-vaginal angle. The curette should never be forced after passing the internal os, as per-

foration is the most serious potential complication of the procedure.

slide 55

slide 56

slide 57

slide 58


10. Once the curette is in place, the suction hosing is attached and the suction machine turned

on. The suction valve on the handle of the hose is then closed. Sixty cm of mercury (Hg) or

greater must be achieved for adequate suction.

11. With the suction on, the curette is rotated several times in one direction, then several times in the

other direction, with slight in-and-out motion. Most of the pressure should be maintained lateral

and forceful jabbing at the uterine fundus avoided, since perforation is a risk. The amount and

nature of tissue that appears in the plastic curette should be carefully observed. Products of con-

ception often appear tan or grey, admixed with blood and clots. Yellowish fluid may be noted. The

curette is withdrawn slowly, avoiding the vaginal side wall while the suction is operating.

12. The suction and rotation sequence can be repeated after inserting the curette into the uterus again.

13. An alternative to electric suction curettage is manual vacuum aspiration, or MVA. This is

accomplished with a simple handheld plastic syringe which generates its own suction

mechanically. This device is inexpensive, easy to use, and requires no electricity. It is particu-

larly appropriate for completions of very early gestations (eg: under eight to 10 weeks men-

strual age.). It may be used in the office setting where a suction machine is not accessible. It

is also appropriate in developing countries where electricity is not available.

14. A light, sharp curettage of the uterus may be done to determine that it is indeed empty, fol-

lowed by one more pass of the suction curette. This is no longer routinely indicated due to the

increased pain and increasing use of postprocedure vaginal ultrasound to confirm completion

in association with examination of tissue.

15. After examination of the tissue it should be sent to pathology for confirmation of diagnosis. To

confirm an intrauterine pregnancy, chorionic villi must be identified.

16. After the uterine aspiration is completed, the patient should be monitored for excessive bleeding.

Misoprostol can be given by the rectal, buccal or sublingual route in a dose of 400 to 800 micro-

grams. Oxytocics can be given as appropriate (Oxytocin 20 units given in a liter of IV fluid or 10

units intramuscular or MethergineR 0.2 mg IM or orally (PO). Transfusions are rarely required.

17. If the patient is Rh negative, 50 mcg (mini dose) of Rh immune globulin should be given.56

18. Doxycycline 100 mg po bid for three days should be routinely given after uterine aspiration to

decrease the likelihood of endometritis.

COMPLICATIONS OF UTERINE ASPIRATION (SUCTION D AND C) Complications of uterine aspiration can occur, as with any surgical procedure. Careful

performance of the procedure, consultation with more experienced physicians when needed, and a

high index of suspicion for identifying complications may prevent complications from occurring.

1. Perforation — Perforation occurs when an instrument passes through the uterine wall. The

diagnosis is usually apparent when a sound or dilator passes through the cervix to a signifi-

cantly greater depth than expected. Occasionally, a suction curette or a sharp curette will draw

maternal abdominal contents such as omentum or bowel out through the cervix. Heavy bleed-

ing, signs of peritonitis, or evidence of intra-abdominal bleeding may also help identify perfora-

tion. If perforation occurs with a blunt instrument such as a sound, and if the D&C has been

completed, then observation alone for a minimum of two hours may suffice. If perforation has

occurred with a sharp instrument such as a curette or with a suction curette, laparoscopy or

slide 59

slides 60, 61

slides 62-67

slide 68

slide 69

slide 70


laparotomy may be indicated. If the uterine aspiration has not been completed at the time the

perforation is identified, it may be completed under either ultrasonic or laparoscopic guidance.

Broad-spectrum antibiotics such as a cephalosporin should be considered for any perforation.

2. Incomplete evacuation — Incomplete evacuation is identified by continued bleeding and

cramping after the procedure, or ultrasound evidence of retained tissue or endometritis, and

may be managed by repeating the procedure. Ultrasonic guidance or general anesthesia is

often helpful. Antibiotics are recommended if the second procedure occurs more than a few

hours after the first. Oxytocics also may be helpful including IV oxytocin, methylergonovine

given IM or orally, or prostaglandin given by various routes.

3. Bleeding — The differential diagnosis of bleeding includes perforation, incomplete evacua-

tion with retained tissue, cervical or uterine injury, or a bleeding disorder. Methylergonovine

(MethergineR) 0.2 mg four times a day for two days is commonly given to patients who may

have more than average bleeding during and after a procedure. An alternative is misoprostol

(CytotecR) 200 ucg four times a day for two days. This drug is not FDA approved for this indi-

cation, but efficacious in practice due to its powerful uterotonic effect.25

4. Infection — Infection may be referred to as septic abortion, endometritis, paraendometritis or

pelvic peritonitis. It is diagnosed by fever, uterine and parauterine tenderness, peritonitis, and an

elevated leukocyte count. The treatment is antibiotics. For ill patients who require hospitalization,

an intravenous cephalosporin or triple antibiotics (ampicillin, gentamycin, and clindamycin or

metronidazole) may be required. Less ill patients may be treated as outpatients. Clear guidelines

for antibiotic regimens are lacking. When tissue is found to be retained, repeating the uterine

evacuation may be necessary. Oxytocics should be given as described in item number two

above. Rarely, in very ill patients, hospitalization and hysterectomy may be necessary.

5. Late Sequelae — Intrauterine synechiae (Asherman’s syndrome) is often discussed but rarely

seen. It is most likely when a suction D&C is performed in the presence of infection, a pro-

longed missed abortion, or postpartum. Incompetent cervix may rarely occur due to cervical

injury. The most common late sequelae to suction D&C are depression and related psycho-

logical reactions to the loss of the pregnancy.

Algorithm: Approach to the patient with first trimester pain or bleeding


Patient Presents with Pain or Bleeding and Positive Urine hCG

PRESUMEECTOPIC

Pelvic mass, fluid in cul-de-sac, or

extrauterine heartbeatPRESUME ECTOPIC

Ultrasound with diagnostic findings:

Embryo with cardiac activity

VIABLE UP

INEVITABLE SAB

Serial hCG

Characteristicsnowstorm pattern

MOLARPREGNANCY

Embryo (>5 mm) without heart beat orSac (>20 mm)

without fetal poleFAILED PREGNANCY

Resuscitation, surgical

evaluationHemodynamically

stable?

Cervix Closed?

US immediately available?

USDiagnostic

?

Counselpatient onoptions:

NormalhCG rise?

Expectantmanagement

Medicalmanagement

Uterineaspiration

Watchful waiting,

Plan routinef/u US

Indication for surgical

managment?

Indication for medical

managment?

ResuscitationSurgical

evaluation

Methotrexateand closefollow-up

Counselpatient onoptions:

Medical management

UterineAspiration

Expectant Managementand follow-up

N

N

N

NN

N

N

Y

Y

Y

Y

Y

Y

Y


SORT: KEY RECOMMENDATIONS FOR PRACTICEClinical Recommendation Evidence Rating ReferencesIn discriminating normal from failing pregnancy, A normal preg-

nancy should exhibit a gestational sac when hCG reaches 1500

to 2000 mIU/mL, a yolk sac when the gestational sac is ten mm

in diameter and cardiac motion when the embryonic crown-rump

length is 5 mm or greater.

C 10

Success of treatment for miscarriage depends on diagnosis.

When the woman has an incomplete miscarriage, nonsurgical

treatments have a high likelihood of success. When the woman

has an embryonic demise or anembryonic pregnancy, misopro-

stol or surgical treatment for considerably more effective than

expectant treatment.

A 23, 24, 25

There is a lack of clear supperiority of expectant versus surgical

management of miscarriage. Therefore, the woman’ preference

should play a dominant role in decision making.

A 59

When the choice is made to treat early pregnancy failure by other

than expectant means, vaginal misoprostol is highly efficacious,

safe and well-accepted by women, with fewer gastrointestinal

side-effects than the oral route.

A 23, 24

Evidence does not support the use of antibiotics in all women

with incomplete abortion.A 27

After any type of first trimester pregnancy loss. Rh negative

women should receive 50 mcg of anti D immune globulin.C 56

Acknowledgement of grief, empathy and reassurance are useful

techniques in counseling women after miscarriage.C 51

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system: http://www.aafp.org/afpsort.xml.


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