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Hydatidiform mole: Management

Authors: Ross S Berkowitz, MD, Donald Peter Goldstein, MD, Neil S Horowitz, MD
Section Editors: Robert L Barbieri, MD, Barbara Goff, MD
Deputy Editors: Sandy J Falk, MD, FACOG, Sadhna R Vora, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2018. | This topic last updated: Apr 14, 2017.

INTRODUCTION — Hydatidiform mole (HM) is part of a group of diseases classified as gestational trophoblastic

disease (GTD), which originate in the placenta and have the potential to locally invade the uterus and
metastasize. The pathogenesis of GTD is unique because the maternal tumor arises from gestational rather than
maternal tissue [1].

HM is made up of two distinct entities, complete hydatidiform mole and partial hydatidiform mole. These differ
on the basis of chromosomal pattern, gross and microscopic histopathology, and clinical presentation and
outcome [2-4]. Molar pregnancies, although benign, are considered to be premalignant because they have the
capability of developing into a malignancy. Malignant disease is referred to as gestational trophoblastic
neoplasia (GTN); the histologic entities included in this group are:

● Invasive mole

● Choriocarcinoma

● Placental site trophoblastic tumor

● Epithelioid trophoblastic tumor

The management of HM will be reviewed here. The pathology of GTD, epidemiology and diagnosis of HM, and
topics regarding GTN are discussed separately:

● (See "Gestational trophoblastic disease: Pathology".)

● (See "Hydatidiform mole: Epidemiology, clinical features, and diagnosis".)

● (See "Gestational trophoblastic neoplasia: Epidemiology, clinical features, diagnosis, staging, and risk
stratification", section on 'Differential diagnosis'.)

● (See "Initial management of low-risk gestational trophoblastic neoplasia".)

● (See "Initial management of high-risk gestational trophoblastic neoplasia".)

● (See "Management of resistant or recurrent gestational trophoblastic neoplasia".)

MANAGEMENT — Surgical uterine evacuation (also referred to as dilation and evacuation or dilation and
curettage) is the mainstay of management for hydatidiform mole (HM), either complete or partial mole.
Hysterectomy is an option in women who have completed childbearing.
Uterine evacuation — Suction curettage is the preferred technique for uterine evacuation, regardless of uterine
size [5].

For women with HM, we suggest uterine evacuation with suction curettage rather than medication-only methods.
Use of medication-only methods for uterine evacuation (misoprostol, mifepristone, oxytocin) is controversial, and
few studies have evaluated the efficacy or safety of this approach [5]. Concern has been raised that inducing
uterine contractions with uterotonics (oxytocin, prostaglandins) will increase the risk of trophoblastic
embolization to the lungs or of metastatic disease. In addition, obtaining a specimen for pathology evaluation is
crucial for confirming the diagnosis of HM and identifying complete versus partial mole. It is more difficult to
obtain a complete specimen with medication-only evacuation.

The only study that evaluated medication-only evacuation for HM (n = 4257) reported that among women who
underwent medication-only evacuation (mainly with prostaglandins), 20 of 77 (26 percent) subsequently required
uterine curettage, and seven were treated with chemotherapy (9 percent compared with 4 to 6 percent after
uterine curettage) [6]. Further study of this issue is needed.

During suction evacuation, we do not use prostaglandins for cervical ripening, based upon the study cited above
[6]. Starting at the time of anesthesia induction, we do administer an oxytocin infusion (10 units in 1 L Ringer
lactate solution at 50 drops/min) to increase myometrial tone and facilitate contraction, and thus decrease blood
loss.

The procedure for suction evacuation consists of mechanical dilation of the cervix, followed by suction
evacuation and then curettage. The technique is the same as for spontaneous or induced abortion. (See
"Spontaneous abortion: Management", section on 'Surgical evacuation'.)

Mechanical dilation of the cervix should be performed gradually to accommodate a cannula diameter
appropriate for the uterine size. Some clinicians advocate the use of laminaria inserted on the previous day in
nullipara to facilitate dilation. During dilatation, brisk bleeding may be encountered due to passage of copious
amounts of blood retained in the endometrial cavity. Evacuation of the uterine contents in a rapid, yet in a
thorough and safe fashion, reduces overall blood loss. After the initiation of suction evacuation, the uterus
generally shrinks rapidly, and bleeding is well controlled. If the uterus is larger than 14 weeks size, the surgeon
may use fundal massage via the abdomen to facilitate uterine contraction. When suction evacuation is thought
to be complete, a gentle sharp curette should be used to remove any residual chorionic tissue. Some surgeons
prefer to use intraoperative sonography to monitor the procedure to determine when evacuation is complete.
Whereas confirmation of the diagnosis of complete mole is usually possible on gross inspection of the
curettings, the appearance of partial mole is frequently non-specific. Bleeding from a molar evacuation may be
substantially more than from a spontaneous, missed, or incomplete abortion. Complete molar tissue will usually
have markedly dilated villi that appear like grape clusters. The changes in partial mole are usually more subtle,
and partial mole may only be suspected or diagnosed based upon the microscopic findings.

Patients at high risk for GTN — Patients at a high risk of gestational trophoblastic neoplasia (GTN) may benefit
from hysterectomy or prophylactic chemotherapy. High-risk features are discussed below. (See 'Gestational
trophoblastic neoplasia' below.)

Hysterectomy — We suggest hysterectomy for women with HM who are ≥40 years and have completed
childbearing. GTN is more likely in this age group. Compared with uterine evacuation, hysterectomy appears to
decrease, but not eliminate, the risk of GTN. (See 'Gestational trophoblastic neoplasia' below.)

The benefit of hysterectomy in this age group was illustrated in a series of 82 women aged 40 to 49 with
complete mole; GTN developed in 37 of 68 (54 percent) women treated with dilation and evacuation alone and in
none of the six patients treated with hysterectomy alone [7]. Markedly elevated human chorionic gonadotropin
(hCG) levels >175,000 mIU/mL appeared to constitute an "ultra high-risk" group for whom prophylactic
chemotherapy or hysterectomy should be especially considered. Eleven (85 percent) of thirteen patients with pre-
evacuation hCG levels >175,000 mIU/mL developed GTN. Similarly, another study that included 22 women aged
50 or older with complete mole found that GTN developed in 9 of 15 patients (60 percent) treated with dilation
and evacuation alone and in none of the seven patients who underwent primary hysterectomy [8].

When counseling patients about treatment options, it is important to inform the patient that hysterectomy
eliminates local invasion and reduces the chance of developing persistent trophoblastic disease, but it does not
prevent all cases of metastatic disease due to occult metastases [9]. Women treated with hysterectomy still
require monitoring, including serial hCG levels [5]. Metastatic GTN develops in 4 percent of patients after uterine
evacuation of a complete hydatidiform mole [1]. (See 'Follow-up' below.)

At time of hysterectomy, the ovaries may be preserved since ovarian metastases are rarely encountered. If
prominent ovarian theca lutein cysts are present, they can be aspirated to reduce the volume and patient
discomfort. Due to the highly vascular nature of the gravid uterus, supracervical hysterectomy is frequently
performed to reduce blood loss and avoid ureteral injury.

Hysterectomy may also be performed for the emergency management of acute hemorrhage at the time of molar
evacuation, although the use of uterine artery embolization has been shown to be successful in managing this
complication [10].

Prophylactic chemotherapy — At our institution, we offer chemotherapy infrequently after evacuation of a

complete hydatidiform mole to high-risk women (see 'Gestational trophoblastic neoplasia' below), but not to
others. It may be particularly useful in patients with high-risk complete mole when hormonal follow-up is either
unavailable or unreliable, as may be the case with adolescents or in certain resource-poor regions, such as some
parts of Asia and Africa [5]. Importantly, chemoprophylaxis does not appear to impact future fertility potential
[11,12]. Both methotrexate and actinomycin D have been used in this setting, and there are no data to suggest
whether one should be the preferred agent. At our center, we generally administer actinomycin D to high-risk
patients.

This practice (otherwise known as prophylactic chemotherapy or chemoprophylaxis) is supported by data that
consistently show that chemotherapy can reduce the risk of subsequent progression or the diagnosis of GTN in
these patients [12-17]. For women at low risk, we do not proceed with prophylactic chemotherapy, but rather
initiate follow-up. (See 'Follow-up' below.)

The administration of prophylactic chemotherapy is supported by a 2012 meta-analysis that included three
randomized trials (n = 613 patients, all diagnosed with complete mole) [13]. The use of prophylactic
chemotherapy was associated with a 63 percent reduction in the risk of GTN (relative risk [RR] 0.37, 95% CI 0.24-
0.57). Despite this finding, issues related to the methodological quality of the trials, including the small size of
the study populations included, limit the wider acceptance of this recommendation. In addition, as noted in this
meta-analysis, the benefit of prophylactic chemotherapy is not entirely clear because other data suggest that
patients who underwent prophylactic chemotherapy and were subsequently diagnosed with GTN experienced a
delay in subsequent diagnosis and required more courses to achieve remission [13].

At the New England Trophoblastic Center, we have treated 93 patients in this fashion, and only 10 (11 percent)
developed persistent disease [12]. Of note, none of these patients had metastatic disease at the time persistent
disease was detected. Six patients were treated with methotrexate for persistent tumor, and of these, five
required only one course of methotrexate to attain remission.

Rh(D) immune globulin — Patients who are Rh(D)-negative should receive anti-D immune globulin at the time of
treatment because the Rh(D) factor is expressed on trophoblast. (See "Prevention of Rhesus (D)
alloimmunization in pregnancy".)

MANAGEMENT OF COMPLICATIONS

Hyperthyroidism — Molar pregnancy-associated hyperthyroidism will resolve with treatment of the gestational

trophoblastic disease (GTD). Some patients will require antithyroid therapy until GTD treatment is complete.
Beta-adrenergic blocking agents may be required before the induction of anesthesia to prevent or rapidly reverse
many of the metabolic and cardiovascular complications of a thyroid storm [18].

The criteria for treatment and approach to therapy are the same as for other human chorionic gonadotropin
(hCG)-mediated hyperthyroidism. (See "Hyperthyroidism during pregnancy: Treatment".)

Ovarian theca lutein cysts — Theca lutein cysts usually regress slowly over two to four months following
evacuation with declining hCG levels. If they are symptomatic, they can be aspirated transabdominally under
ultrasound guidance. Theca lutein cysts may cause adnexal torsion or, rarely, they rupture spontaneously. In such
cases, they can be managed laparoscopically [19]. (See "Ovarian and fallopian tube torsion" and "Evaluation and
management of ruptured ovarian cyst".)

Preeclampsia — Preeclampsia associated with complete molar pregnancy resolves promptly after molar
evacuation and usually does not require medical management.

Cardiopulmonary symptoms — In women treated in the first trimester, cardiopulmonary symptoms are rare
[20,21]. After uterine evacuation for complete hydatidiform mole in the second trimester, approximately 2 percent
of patients used to develop cardiopulmonary symptoms, including chest pain, dyspnea, tachypnea, and
tachycardia [20]. Auscultation of the chest usually reveals diffuse rales, and the chest radiograph often
demonstrates bilateral pulmonary infiltrates. The signs and symptoms usually resolve within 72 hours after
evacuation with cardiopulmonary support.

Respiratory distress is usually attributed to trophoblastic embolization, but can also be due to the
cardiopulmonary complications of thyroid storm, toxemia, and massive fluid replacement. The presence of
pulmonary infiltrates can sometimes be misinterpreted as metastases, for which chemotherapy is
inappropriately administered. In most cases, the infiltrates will resolve over 48 to 72 hours as the hCG level
decreases [22]. The presence of pulmonary nodule(s) after molar evacuation in the face of falling hCG levels
does not require chemotherapy. Trophoblastic emboli usually resolve spontaneously as long as the hCG level
ultimately normalizes.

FOLLOW-UP — Follow-up of treatment of hydatidiform mole (HM) consists of measurement of serial serum

human chorionic gonadotropin (hCG) levels, until an undetectable level is reached and is maintained for several
months (algorithm 1).

Poor compliance with post-molar surveillance and treatment protocols is associated with poorer outcomes due
to advanced disease. In the United States, indigent women treated at urban, public hospitals are the group most
likely to fail to comply with standard protocols for a number of reasons, including cost, transportation issues, and
childcare requirements [23]. Patient education is crucial to help patients to understand and comply with
surveillance protocols.

Serial hCG — All patients with HM should be monitored with serial serum hCG testing values after evacuation to
evaluate for postmolar gestational trophoblastic neoplasia (GTN).

Surveillance protocol — Guidelines from the American College of Obstetricians and Gynecologists advise the
following protocol [24]:

● Every week until non-detectable for three weeks, then

 ● Every month for six months – If the hCG remains undetectable for six months, then the patient may resume
trying to become pregnant, if she wishes.

Shorter duration of monitoring — Many patients find the six-month period of follow-up difficult to
complete. Women may wish to begin attempting another pregnancy sooner, particularly those over age 35.
Furthermore, weekly or monthly hCG testing is anxiety-provoking for many women, expensive, and inconvenient,
making non-compliance common.

A shorter period of hCG monitoring appears to be safe [25-33]. The risk of GTN is <1 percent after an
undetectable hCG level is attained, based upon data from several thousand women from multiple institutions,
including the Charing Cross Hospital, University of Texas Southwestern, New England Trophoblastic Disease
Center (NETDC), and centers in Hungary, Australia, Brazil, and the Netherlands [26-33]. This was illustrated in a
large series of women with molar pregnancy (n = 22,053) from Charing Cross Hospital in England; among women
in whom the hCG normalized, only 1 in 760 developed GTN [34]. If the hCG normalized within 56 days after
evacuation, the risk of GTN was 1 in 1536 compared with 1 in 464 when hCG normalized in greater than 56 days.
The mean time to first raised hCG level after normalization was 449 and 462 days in the <56 and >56 day groups,
respectively. Due to the long interval to the hCG rise after normalization, it is possible that some of these cases
were new molar conceptions. Similarly [26], in a series of 1029 patients with complete mole treated with
evacuation, no patient developed GTN after the hCG level became undetectable using an assay sensitive to <5
mIU/mL.

Patients with partial mole may be particularly suitable for shortened duration of hCG surveillance because of
their low risk of persistence [30]. As an example [32], in a prospective cohort study (n = 2008) of patients
registered at the French Trophoblastic Disease Centre, the risk of postmolar GTN after hCG normalization was
0.34 percent after complete mole, 0 percent after partial mole, and 0.36 percent after a multiple pregnancy with
co-existing mole. Similarly, in a study involving 284 women with partial mole, none of the patients developed GTN
following spontaneous decline and normalization of the hCG level [28].

On the basis of these data, it may be reasonable to abbreviate hCG follow-up for women with both complete
mole and partial mole without appreciably increasing the risk of delayed diagnosis of GTN. It is the current policy
at our center, the NETDC, to allow patients following either a complete or partial mole to become pregnant after
achieving three consecutive weekly followed by three consecutive monthly undetectable hCG levels.

It is possible to utilize hCG regression curves to predict a patient’s risk of developing GTN after molar evacuation
[35-37]. In one study, an hCG level of >199 mIU/mL in the third through eighth week following partial mole
evacuation was associated with at least a 35 percent risk of GTN [38]. Similarly, another study reported that
women after a complete mole whose hCG levels were <200 mIU/mL in the fourth week after evacuation or <100
mIU/mL in the sixth week after evacuation had a risk of persistence below 9 percent. An hCG level >2000
mIU/mL in the fourth week after evacuation was associated with a 63.8 percent risk of developing persistent
disease [27].

Diagnosis of GTN — Following evacuation of a complete or partial molar pregnancy, if hCG levels rise or
remain elevated over several weeks, the patient is classified as having GTN. The diagnosis of postmolar GTN is
based upon the following International Federation of Gynecology and Obstetrics (FIGO) criteria [39-41]:

● hCG levels plateau (remain within ±10 percent of the previous result) across four measurements over a
three-week period (eg, days 1, 7, 14, and 21)  

● hCG level increases >10 percent across three values over a two-week duration (eg, measurements on days 1,
7, and 14, increase is >10 percent from day 1 to day 14)

● Persistence of detectable serum hCG for more than six months after molar evacuation
There are internationally accepted criteria to make the diagnosis of GTN for women who had a prior molar
pregnancy. However, FIGO also accepts the diagnosis of GTN based on a histologic diagnosis of
choriocarcinoma or invasive mole (eg, made by examination of uterine curettings) and/or the identification of
clinical or radiological evidence of metastases.

Although FIGO guidelines recommend treatment in patients with persistent hCG levels six months after molar
pregnancy, a group from Charing Cross Hospital reported on 76 patients from a cohort of 13,960 with HMs who
had persistently elevated but declining hCG levels six months after evacuation. In this study, 66 (87 percent)
patients were treated expectantly, and only 13 percent required chemotherapy treatment [42]. Similarly, among
12,526 Brazilian patients with molar pregnancy, 96 (0.8 percent) had persistent but falling hCG at six months
after evacuation [43]. Expectant management was followed in 81 patients and 65 (80.2 percent) achieved
spontaneous remission, and in 16 who developed late GTN they did not have any worsening of their extent of
disease.

The evaluation and diagnosis of GTN is discussed in detail separately. (See "Gestational trophoblastic neoplasia:
Epidemiology, clinical features, diagnosis, staging, and risk stratification", section on 'Diagnostic evaluation' and
"Gestational trophoblastic neoplasia: Epidemiology, clinical features, diagnosis, staging, and risk stratification",
section on 'Diagnosis'.)

Persistent low hCG (quiescent GTN) — On rare occasions following molar evacuation, the hCG level will fail to
normalize and remain elevated at low levels (<200 mIU/mL). One cause of persistent (present for at least three
months) low-level hCG is quiescent GTN, also referred to as inactive GTN.

Quiescent GTN is a persistently low level of hCG in the absence of any clinical or radiological evidence of GTN.
While quiescent GTN most commonly occurs after a complete mole, it may develop after partial mole, invasive
mole, or choriocarcinoma. This condition is thought to be due to the presence of a small focus of highly
differentiated, non-invasive syncytiotrophoblast cells that produce small stable amounts of hCG and usually do
not progress to invasive disease as long as cytotrophoblast or intermediate cells are absent [44].

Quiescent GTN is characterized by the following: (1) foci of disease are not readily identifiable clinically, and (2)
hCG level is unresponsive to therapy, presumably because the growth cycle of these cells is long and comparable
to normal cells. Patients with quiescent GTN should not be treated with chemotherapy, but close follow-up is
indicated because 6 to 10 percent will eventually develop active GTN, requiring treatment [45-47].

The measurement of hyperglycosylated hCG (hCG-H) has been proposed for surveillance in patients with
quiescent GTN [46,48]. hCG-H is a glycoprotein produced by cytotrophoblast cells and is associated with
trophoblast invasion, growth of cytotrophoblast cells, and overall promotion of placental implantation. It is
thought to be a promoter of choriocarcinoma growth and tumorigenesis, and is the main form of hCG produced
in active GTN.

The presence of low levels of hCG-H indicates the presence of quiescent GTN. Increasing levels of hCG-H
indicate the development of active GTN that requires treatment [44,45].

Patients with quiescent GTN should be monitored with monthly hCG testing and advised to avoid pregnancy [49].
Active GTN should be diagnosed, and treated appropriately, if hCG-H rises to greater than 20 percent of total hCG
or if total hCG has two doublings [48,50,51]. (See "Initial management of low-risk gestational trophoblastic
neoplasia".)

There are several other etiologies of a persistent low-level hCG, including pituitary gland hCG production
particularly in perimenopausal women. The differential diagnosis of persistent low hCG is discussed in detail
separately. (See "Human chorionic gonadotropin: Testing in pregnancy and gestational trophoblastic disease and
causes of low persistent levels", section on 'Causes and evaluation of persistent low levels of hCG'.)
Contraception — Women with molar pregnancy must be advised to use reliable contraception during the entire
interval of hCG monitoring. A new pregnancy during this period would make it difficult or impossible to interpret
hCG results and would complicate management. Options include hormonal contraception or barrier methods.
Depot medroxyprogesterone is an option for women who have difficulty complying with contraceptive use [23].
An intrauterine device should not be used before the hCG normalizes because of the risk of uterine perforation
due to subinvolution of the uterus or invasive mole.

Historically, women were advised to use only barrier contraception based upon a concern that hormonal
contraceptives may increase the risk of GTN [52]. Some data suggest that this increased risk was associated
with estrogen doses of 50 mcg or higher in older oral contraceptives [53]. However, the safety of postmolar use
of oral contraceptives has been demonstrated in three reports, including two randomized trials [54-56]. The
largest was a Gynecologic Oncology Group randomized trial (n = 266) that assigned patients to oral
contraceptives or barrier contraception after evacuation of an HM [55]. No significant difference in the rate of
postmolar trophoblastic disease was found between the groups; in fact, the oral contraceptive group had a lower
rate (23 versus 33 percent). The median time to spontaneous regression in the oral contraceptives group was
nine weeks, whereas the median time to regression in the barrier group was 10 weeks. Twice as many patients in
the barrier group became pregnant in the immediate follow-up period. In addition, a systematic review of seven
studies including 1533 women reported that all but one study found no increased risk of GTN with postmolar use
of oral contraceptives [57].

OUTCOME

Gestational trophoblastic neoplasia — Hydatidiform mole (HM) is well recognized to have a risk of developing
invasive disease, referred to as gestational trophoblastic neoplasia (GTN).

The reported incidence of GTN after each type of molar pregnancy is [9,58-61]:

● Complete mole (15 to 20 percent)

● Partial mole (1 to 5 percent)

The wide range of the reported incidence of postmolar GTN results from differences in diagnostic criteria and
the size of the population studied. Among women with molar pregnancy, the risk factors for developing GTN
include: (1) complete mole with signs of trophoblastic proliferation (uterine size greater than gestational age,
serum human chorionic gonadotropin [hCG] levels >100,000 mIU/mL); (2) ovarian theca lutein cysts >6 cm in
diameter; and (3) age >35 to 40 years.

The increased risk in complete mole with signs of marked trophoblastic proliferation was illustrated by data from
our center, the New England Trophoblastic Disease Center (NETDC), from 858 women with complete mole [5].
The presence versus absence of trophoblastic proliferative signs (uterine size greater than gestational age,
serum hCG levels >100,000 mIU/mL, and ovarian theca lutein cysts >6 cm in diameter) was associated with
significantly higher rates of uterine invasion (31.0 versus 3.4 percent) and metastases (8.8 versus 0.6 percent).
Since complete moles are currently usually diagnosed in the first trimester, the classical signs of late molar
pregnancy are not commonly encountered. Despite early diagnosis, however, the incidence of postmolar GTN is
unchanged. First trimester complete moles still frequently present with high hCG values, and high hCG values in
first trimester complete moles are still associated with the development of GTN.

Older patients with complete mole are also at increased risk of developing a postmolar tumor. Studies have
found that 33 to 60 percent of women over age 40 with complete mole develop persistent disease [7,62,63].
Other studies have reported that 53 to 56 percent of women over 50 with complete moles developed postmolar
tumor [8,64].
Complete moles are more commonly aneuploid in older women, and aneuploidy may be a risk factor for GTN
[65]. One study reported that 10 of 13 (77 percent) aneuploid complete moles developed persistent tumor [66].

In contrast to patients with advanced age, adolescents (<age 20) do not appear to have a higher risk of
developing postmolar disease. As an example, one study of the clinical presentation and outcome in 220
adolescent patients with complete mole noted a significantly decreased risk of developing GTN [67].

For partial mole, no risk factors for developing GTN have been identified [68]. After partial mole, persistent tumor
is generally non-metastatic [5]. As an example, 11 studies including 7579 patients with partial mole show that
only 76 (1.0 percent) women developed persistent tumor and only nine (0.1 percent) had metastases [2,3,68-76].

Patients with repeat molar pregnancy are at an increased risk of developing persistent tumor. One study reported
a threefold increased risk of postmolar tumor in patients with a repeat molar pregnancy [77]. Among 39 patients
with two molar pregnancies managed at the NETDC from 1965 to 2013, persistent tumor developed following the
first mole in 4 of 20 (20 percent) complete moles and following the second mole, in 8 of 20 (40 percent)
complete moles, and in 2 of 17 (11.7 percent) partial moles [78].

Subsequent pregnancy — In general, patients with both complete mole and partial mole can anticipate normal
future reproductive outcomes.

At the NETDC between 1965 and 2013, obstetric outcomes included [78]:

● Patients with complete mole had 1388 subsequent pregnancies: 949 (68.4 percent) term live births, 103 (7.4
percent) premature deliveries, seven (0.5 percent) stillbirths, 256 (18.4 percent) spontaneous abortions, and
11 (0.8 percent) ectopic pregnancies. Major and minor congenital anomalies were detected in 40 (3.8
percent) infants.

● Patients with partial mole had 357 subsequent pregnancies: 260 (72.8 percent) term live births, eight (2.2
percent) premature deliveries, one (0.3 percent) stillbirth, 64 (17.9 percent) spontaneous abortions, and two
(0.6 percent) ectopic pregnancies. Major and minor congenital anomalies were diagnosed in only four (1.5
percent) infants.

These rates are similar to other institutions [79,80].

Repeat molar pregnancy — Women with a prior HM are at increased risk of developing subsequent HM
compared with the general population [81].

Estimates of the risk of subsequent HM are:

● After one molar pregnancy (1 to 1.9 percent) [79,80,82]

● After two molar pregnancies (15 to 17.5 percent) [78,79]

A single-institution series reported that among 2578 women with complete mole, the subsequent pregnancy was
molar in 27 (1.9 percent), including 22 (81 percent) complete moles and five (19 percent) partial moles [80].
Among 2627 patients with a partial mole, the subsequent pregnancy was molar in 25 (1.7 percent), including 17
(68 percent) partial moles and eight (32 percent) complete moles. The overall risk of molar pregnancy was 1.8
percent, which represented a 20-fold increase compared with the general population. Among 27 cases with
repeat complete mole, three had later molar pregnancies, indicating a recurrence rate after two previous
complete moles of 11 percent.

At the NETDC between 1965 and 2013, following two molar pregnancies, 25 patients had 40 subsequent
pregnancies: seven (17.5 percent) molar pregnancies (six complete, one partial), 25 (62.5 percent) term live
births, one intrauterine fetal demise (2.5 percent), three spontaneous abortions (7.5 percent), three induced
abortions (7.5 percent), and one ectopic pregnancy (2.5 percent) [78].

Obstetric management — Due to the risk of recurrent HM, in our practice, we advise patients with a prior HM
to have a first trimester ultrasound to confirm normal gestational development in subsequent pregnancies.
Additionally, we measure a serum hCG at six weeks after the completion of any type of future pregnancy (eg,
term delivery, spontaneous abortion, induced abortion) to exclude choriocarcinoma. After preterm or term
deliveries in patients with prior molar pregnancy or GTN, the placenta should be carefully examined and sent to
pathology if any abnormalities are present. Additionally, all products of conception from miscarriages or
abortions should be examined pathologically.

SUMMARY AND RECOMMENDATIONS

● Hydatidiform mole (HM) is part of a group of diseases classified as gestational trophoblastic disease (GTD),
which originate in the placenta and have the potential to locally invade the uterus and metastasize. (See
'Introduction' above.)

● Uterine evacuation is the mainstay of treatment for HM. For women with HM, we suggest uterine evacuation
with suction curettage rather than medication-only methods (Grade 2C). (See 'Uterine evacuation' above.)

● For women with HM who are age ≥40 years and have completed childbearing, we suggest hysterectomy
rather than uterine evacuation (Grade 2C). (See 'Hysterectomy' above.)

● Follow-up of treatment of HM consists of measurement of serial weekly serum quantitative human chorionic
gonadotropin (hCG), until an undetectable level is reached (algorithm 1). (See 'Surveillance protocol' above.)

● Following evacuation of a complete or partial molar pregnancy, if hCG levels rise or remain elevated over
several weeks, the patient is classified as having gestational trophoblastic neoplasia (GTN). The diagnosis
of post-molar GTN is based upon the International Federation of Gynecology and Obstetrics (FIGO) criteria.
(See 'Diagnosis of GTN' above.)

● Women with molar pregnancy must be advised to use reliable contraception during the entire interval of hCG
monitoring. A new pregnancy during this period would make it difficult or impossible to interpret hCG results
and would complicate management. Options include hormonal contraception or barrier methods. (See
'Contraception' above.)

● Estimates of the risk of recurrent HM are: after one molar pregnancy (1 to 1.9 percent), and after two molar
pregnancies (15 to 17.5 percent). (See 'Repeat molar pregnancy' above.)

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Topic 3194 Version 16.0

GRAPHICS

Molar pregnancy management algorithm

* Beta-human chorionic gonadotropin.

¶ Patients should use contraception until follow-up is complete.
Δ A decreasing β-hCG is defined as a level that decreases >10 percent compared with the previous result, and continues to meet
this criterion across four values during a three-week period.
◊ An increasing β-hCG is defined as a level that increases >10 percent compared with the previous result, and continues to meet
this criterion across three values during a two-week period.
§ An unchanged β-hCG is defined as a level that remains with +/– 10 percent compared with the previous result, and continues to
meet this criterion across four values during a three-week period.
¥ After achieving one undetectable β-hCG value (<5 mIU/mL), the risk of developing gestational trophoblastic neoplasia is <1
percent. American College of Obstetrician and Gynecology guidelines advise that after the β-hCG is undetectable, to continue to
measure β-hCG monthly for six months. Based on the extremely low risk of a rise in hCG after it becomes undetectable, in our
practice, we continue monthly β-hCG follow-up for three months and then follow-up is complete.

Graphic 105721 Version 1.0

Contributor Disclosures
Ross S Berkowitz, MD Nothing to disclose Donald Peter Goldstein, MD Nothing to disclose Neil S Horowitz,
MD Grant/Research/Clinical Trial Support: TRACON Pharmaceuticals [Gestational trophoblastic neoplasia
(TRC105)]. Robert L Barbieri, MD Nothing to disclose Barbara Goff, MD Employment (Spouse): Lilly [General
oncology (Gemcitabine, pemetrexed)] - No relevant conflict on topics. Sandy J Falk, MD, FACOG Nothing to
disclose Sadhna R Vora, MD Nothing to disclose

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