CC BY-NC-ND 4.0 · AJP Rep 2022; 12(01): e96-e107
DOI: 10.1055/a-1678-3563
Case Report

Complete Molar Pregnancies with a Coexisting Fetus: Pregnancy Outcomes and Review of Literature

1   Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Maternal Fetal Medicine, University of California San Francisco, San Francisco, California
,
Kerry Holliman
2   Austin Maternal-Fetal Medicine, Austin, Texas
,
Michelle Debbink
3   Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of Utah, Salt Lake City, Utah
,
Lori Day
4   Obstetrix Medical Group, Beacon Memorial Hospital, Division of Maternal Fetal Medicine, South Bend, Indiana
,
Krista Mehlhaff
5   Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland
,
Lisa Gill
6   Department of Obstetrics, Gynecology, and Women's Health, Division of Maternal Fetal Medicine, University of Minnesota, Minneapolis, Minnesota
,
Cara Heuser
7   Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Intermountain Healthcare and University of Utah, Salt Lake City, Utah
,
Alisa Kachikis
8   Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Washington, Seattle, Washington
,
Kristine Strickland
9   Prevea Health, Maternal Fetal Medicine, Green Bay, Wisconsin
,
Justin Tureson
10   Department of Obstetrics and Gynecology, Naval Readiness and Training Command, Twentynine Palms, Twentynine Palms, California
,
Jessica Shank
11   Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Tulane University School of Medicine, New Orleans, Louisiana
,
Rachel Pilliod
12   Department of Obstetrics and Gynecology, Oregon Health & Science University, Division of Maternal Fetal Medicine, Portland, Oregon
,
Chitra Iyer
13   Obstetrix Medical Group of Texas, Fort Worth, Texas
,
2   Austin Maternal-Fetal Medicine, Austin, Texas
› Author Affiliations
 

Abstract

Objective The objective of the study was to review the obstetric outcomes of complete hydatidiform molar pregnancies with a coexisting fetus (CHMCF), a rare clinical entity that is not well described.

Materials and Methods We performed a retrospective case series with pathology-confirmed HMCF. The cases were collected via solicitation through a private maternal-fetal medicine physician group on social media. Each contributing institution from across the United States (n = 9) obtained written informed consent from the patients directly, obtained institutional data transfer agreements as required, and transmitted the data using a Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliant modality. Data collected included maternal, fetal/genetic, placental, and delivery characteristics. For descriptive analysis, continuous variables were reported as median with standard deviation and range.

Results Nine institutions contributed to the 14 cases collected. Nine (64%) cases of CHMCF were a product of assisted reproductive technology and one case was trizygotic. The median gestational age at diagnosis was 12 weeks and 2 days (9 weeks–19 weeks and 4 days), and over half were diagnosed in the first trimester. The median human chorionic gonadotropin (hCG) at diagnosis was 355,494 mIU/mL (49,770–700,486 mIU/mL). Placental mass size universally enlarged over the surveillance period. When invasive testing was performed, insufficient sample or no growth was noted in 40% of the sampled cases. Antenatal complications occurred in all delivered patients, with postpartum hemorrhage (71%) and hypertensive disorders of pregnancy (29%) being the most frequent outcomes. Delivery outcomes were variable. Four patients developed gestational trophoblastic neoplasia.

Conclusion This series is the largest report of obstetric outcomes for CHMCF to date and highlights the need to counsel patients about the severe maternal and fetal complications in continuing pregnancies, including progression to gestational trophoblastic neoplastic disease.

Key Points

  • CHMCF is a rare obstetric complication and may be associated with the use of assisted reproductive technology.

  • Universally, patients with CHMCF who elected to manage expectantly developed antenatal complications.

  • The risk of developing gestational trophoblastic neoplasia after CHMCF is high, and termination of the pregnancy did not decrease this risk.


#

Ultrasonographic evidence of an enlarged multicystic placenta with a normal-appearing fetus is an uncommon finding during routine surveillance of pregnancy. The differential diagnoses of these features include partial hydatidiform molar pregnancy with a coexisting fetus (HMCF) or complete HMCF (CHMCF), placental mesenchymal dysplasia (PMD), placental infarcts, chorioangioma, subchorionic hematoma, placental cysts, and placenta accreta spectrum (PAS) disorders. In the context of an otherwise normal-appearing fetus, the obstetrical course and postpartum follow-up of these conditions are vastly different ([Table 1]).

Table 1

Comparison of the clinical findings of placental mesenchymal dysplasia (PMD), complete hydatidiform mole (CHM), and partial hydatidiform mole (PHM)

PMD

CHM

PHM

Ultrasound findings

Enlarged multicystic placenta with anechoic regions (“moth-eaten” appearance)

Findings widely distributed, large edematous villi

Fetus[18]

 • Can be unremarkable

 • FGR (50%)

 • IUFD or neonatal death (43%)

 • Consider BWS findings: macroglossia, omphalocele, genitourinary abnormalities, overgrowth, polyhydramnios

• Coexisting fetus can be unremarkable

• May be structurally abnormal triploid fetus[19]

Pathology

 • Enlarged stem villi with loose connective tissue and cisternlike formations

 • Absent trophoblastic changes

• Hydropic swelling of villi

• Diffuse trophoblastic hyperplasia

• Diffuse and marked trophoblastic atypia at the molar implantation site

• Focal trophoblastic hyperplasia

• Marked variability in the size and degree of swelling, and cavitation of the villi

• Marked scalloping and prominent stromal trophoblastic inclusion in the villi

• Focal and mild trophoblastic atypia at molar implantation site

Associated maternal morbidities

None identified

• GTN

• Preeclampsia

• Choriocarcinoma

1. GTN

2. Preeclampsia

3. Choriocarcinoma

Cytogenetics

 • Normal karyotype (89%)

 • 46 XX (78%), 46 XY (22%)

 • BWS: confirmed or suspected (23%)[20]

• 46 XX: haploid 23 X sperm duplicates its own chromosomes[21] [22]

• 46 XY: ova penetrated by 2 sperm (dispermy), 46 XY[23]

• Triploidy: extra haploid sperm[4]

Clinical presentation

No definitive clinical characteristics, but may be associated with preterm labor, secondary to amniotic fluid abnormalities

• Vaginal bleeding

• Size greater than dates

• Theca lutein cysts

• Hyperemesis

• Preeclampsia

• Hyperthyroidism

• Pulmonary edema

• Respiratory distress

• Commonly diagnosed after missed or incomplete abortion, based on pathology

Abbreviations: BWS, Beckwith–Wiedemann syndrome; CHM, complete hydatidiform mole; FGR, fetal growth restriction; GTN, gestational trophoblastic neoplasia; IUFD, intrauterine fetal demise; PHM, partial hydatidiform mole; PMD, placental mesenchymal dysplasia.


In the case of a CHMCF, it is especially important to have an accurate diagnosis. This rare condition, affecting 20,000 to 100,000 pregnancies,[1] [2] is fraught with potential maternal complications, such as hemorrhage, preeclampsia, and preterm delivery of the viable coexisting fetus. Persistent gestational trophoblastic neoplasia (GTN) is also seen more frequently in CHMCF, when compared with a single complete mole, and termination of the pregnancy has not been shown to decrease this risk.[1] [3] [4]

Although there have been large case series reported on CHMCF, they have focused mainly on outcomes as they relate to the GTN associated with this condition.[1] [3] [4] In these reports, the use of artificial reproductive technology (ART) was either not reported or, when reported, did not account for a majority of cases (13%). An increased use of ART over the past several decades may affect the prevalence of CHMCF and so obstetricians should be cognizant of this condition and its associated ante-, intra-, and postpartum risks. When an isolated complete molar pregnancy is noted, evacuation of the premalignant molar tissue is recommended. However, in the case of a CHMCF, a woman may elect to be managed expectantly to prolong the pregnancy. Here, we provide the first multicenter series of CHMCF reporting detailed accounts of the diagnosis, pregnancy outcomes, and postpartum follow-up, as well as a review of existing literature, to aid in the counseling of this at-risk cohort of pregnant women.

Materials and Methods

A retrospective analysis of women with CHMCF pregnancies was performed. The cases were collected via solicitation through a private maternal-fetal medicine physician group on social media. Each contributing institution from across the United States (n = 9) obtained written informed consent from the patient(s) directly, obtained institutional data transfer agreements as requested, and transmitted the data using a Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliant modality.

Electronic records were reviewed and the following data were identified: maternal characteristics (age, gravidity, parity, prepregnancy body mass index, race, and prior maternal comorbidities); mode of conception; gestational age at diagnosis; human chorionic gonadotropin (hCG) at diagnosis; zygosity of the pregnancy; screening assessments (including laboratory and imaging); antenatal genetics (procedure type, results, and timing); and size of placental mass as measured by prenatal ultrasonography. Maternal complications including vaginal bleeding, hyperthyroidism, and hypertensive disorders of pregnancy were noted. The timing, mode, and indication for delivery, as well as the estimated blood loss or complications of delivery or procedure were recorded. Postnatal confirmation of genetics and pathology, postpartum follow-up, including hCG trend and time to nadir, diagnosis of GTN, and subsequent treatments were identified.

Fetal and neonatal outcomes recorded included any structural anomalies noted prenatally, intrauterine fetal growth restriction, intrauterine or neonatal fetal demise, and neonatal birthweight.

Statistical Analysis

For descriptive analysis, continuous variables were reported as median with standard deviation and range. Categorical variables were reported as proportions.


#
#

Results

After solicitation via social media, nine institutions were able to obtain patient consent and contributed 14 cases in total. Clinical characteristics of the patients are delineated in [Table 2].

Table 2

Patient characteristics and comorbidities

Case no.

Age (y)

G/P

Conception

BMI

Race/ethnicity

Comorbidities

1

30

2/1001

OI/GnTP/IUI

20.8

Caucasian

None

2

27

1/0

OI/CC

26.7

Caucasian

PCOS, seizure disorder on Lamictal

3

36

1/0

OI/CC/IUI

30.6

Caucasian

Lupus on Plaquenil

4

32

2/1001

Spontaneous

23.0

Caucasian

None

5

26

2/0010

Spontaneous

34.0

Caucasian/Asian

Anxiety, depression

6

29

2/1001

OI/GnTP

22.6

Caucasian

Chronic HTN

7

27

1/0

OI/CC

36.0

Caucasian

None

8

35

2/1001

Spontaneous

31.6

White

h/o Roux-en-Y, anemia, h/o gestational HTN

9

28

8/2052

OI/GnTP

28.2

White

Migraine, PCOS with infertility

10

28

3/1011

Spontaneous

19.4

Arab-American

h/o 2nd trimester IUFD (19 wk)

11

32

4/2012

Spontaneous

21.0

White

h/o bilateral PE, h/o 2nd trimester IUFD (16 wk)

12

38

2/1001

IVF

22.9

Asian

seizures on levetiracetam and lamotrigine

13

34

3/1011

COH/IUI

24.0

Caucasian

None

14

33

1/0

IVF

21.0

Asian

Asthma

Abbreviations: BMI, body mass index; CC, clomiphene citrate; COH, controlled ovarian hyperstimulation; GnTP, gonadotropin; h/o, history of; HTN, hypertension; IUI, intrauterine insemination; IUFD, intrauterine fetal demise; IVF, in vitro fertilization; OI, ovulation induction; PCOS, polycystic ovarian syndrome; PE, pulmonary embolism.


Of the cases presented here, 64% were the product of ART: 29% ovulation induction alone, 21% ovulation induction with intrauterine insemination, and 14% in vitro fertilization. Only five cases (36%) were due to spontaneous conception. The median gestational age at diagnosis was 12 weeks and 2 days (9 weeks–19 weeks and 4 days), with 64% (n = 9) diagnosed in the first trimester and the remaining diagnosed by 20 weeks of gestation. Upon either diagnosis or suspicion of diagnosis, all patients were referred to a maternal-fetal medicine specialist, who was involved in the remainder of the pregnancy. The median hCG at diagnosis was 355,494 mIU/mL (49,770–700,486 mIU/mL). The largest dimension of the placental mass at the time of diagnosis varied, ranging from 3.5 to 12 cm. The size of the placental mass universally enlarged over the antenatal surveillance period. Antenatal genetic analysis was performed in 10 of the 14 cases. Insufficient sample or no growth of the sample from either amniocentesis (n = 5) or chorionic villous sampling (CVS; n = 5) was a common finding, occurring in 40% of cases sampled (n = 4).

In the reported dizygotic CHMCF pregnancies, no malformations were identified. The one case of trizygotic CHMCF pregnancy had a complete mole, a coexisting structurally normal fetus, and a partial molar pregnancy with cystic hygroma and complex congenital heart defect.

Antenatal management and complications are described in [Table 3]. Universally, patients with CHMCF experienced some form of antenatal complication, including vaginal bleeding (10; 71%), hypertensive disorder of pregnancy (4; 28.9%), pulmonary edema (1; 0.7%), and hyperthyroidism (1; 0.7%). Of the patients with vaginal bleeding, 4 of 10 (40%) required admission and/or transfusion. The case of hyperthyroidism required medical treatment with antithyroid medications and ultimately resulted in termination of pregnancy.

Table 3

Antenatal management and pregnancy outcomes

Case no.

Planned management

Complications

GA at delivery

Delivery type

EBL (mL)

Genetics prenatal

hCG trend

Subsequent Dx

Treatment

1

Expectant (initially declined termination)

Serial growth ultrasounds

Termination when HELLP

SAB of twin B at 14 wk

HELLP at 16 wk

16 wk and 6 d

D&E

1,000

70 XXXY

Plateau at 8 wk PP

Metastatic GTN (FIGO stage 3) lung nodules

IV MTX

2

Expectant (declined termination)

Serial growth ultrasounds

VB (admission)

Anemia

Preterm labor

20 wk and 2 d

SVD

300

None

Nadir by 12 wk PP

None

None

3

Expectant

VB

Tachycardia

Palpitations

13 wk and 3 d

D&E

200

T22

Nadir by 13 wk PP

None

None

4

Expectant (declined termination)

VB

Hyperthyroidism (admission) Anemia/transfusion (2 U pRBC)

PEC with severe features

Hemorrhage with passage of molar tissue

Intraoperative transfusion (3 U pRBC)

Hysterectomy due to postpartum hemorrhage

24 wk and 5 d

Emergent classical CD

2,500

None

Nadir by 8 wk PP, then increased

Metastatic GTN FIGO stage 4

IV MTX

then IV dactinomycin

5

Desired termination

Pulmonary edema

21 wk and 1 d

D&E

125

None

Nadir by 7 wk PP

None

None

6

Expectant

Serial laboratories

Serial growth ultrasounds

SAB of twin A

VB

Superimposed PEC with severe features

34 wk and 5 d

SVD

250

None

Nadir by 4 wk PP

None

None

7

Expectant

Serial laboratories

Serial growth ultrasounds

VB

GHTN

34 wk and 2 d

Classical CD

1,000

None

Not available

None

None

8

Expectant

Serial laboratories

Serial growth ultrasounds

VB and anemia

PTL

Postpartum hemorrhage

32 wk and 2 d

Urgent classical CD due to funic presentation

1,500

None

Nadir by 7 wk PP

None

None

9

Expectant

Serial laboratories

Serial growth ultrasounds

VB

PTL

HTN

Fever and tachycardia (unclear diagnosis)

28 wk and 3 d

SVD

350

None

Nadir by 10 wk PP

None

None

10

Desired termination

Abnormal TFTs with palpitations (started methimazole)

Bilateral ovarian masses (largest 10 × 9 × 8 cm)

15 wk

D&E

250

None

Nadir by 4 wk PP then elevated

Metastatic GTN FIGO stage 3

IV MTX and leucovorin

11

Expectant

Serial laboratories

Serial growth ultrasounds

VB

PTL

34 wk and 2 d

SVD

300

None

Nadir by 6 wk PP

None

None

12

Desired termination

VB

16 wk and 6 d

D&E

250

None

Nadir by 12 wk PP

None

None

13

Desired termination

None

15 wk

D&C

50

None

Plateau at 2 wk PP

GTN

FIGO stage 1

IV MTX

14

Expectant

Chorioamnionitis

Postpartum hemorrhage

17 wk and 5 d

SVD

500

46 XX

Nadir by 12 wk PP

None

None

Abbreviations: CD, cesarean delivery; D&C, dilation and curettage; D&E, dilation and evacuation; FIGO, International Federation of Gynecology and Obstetrics; GA, gestational age; GTD, gestational trophoblastic disease; GTN, gestational hypertension; HELLP, hemolysis, elevated liver enzymes, low platelets; HTN, hypertension; IV, intravenous; MTX, methotrexate; PTL, preterm labor; PP, postpartum; SAB, spontaneous abortion; SVD, spontaneous vaginal delivery; VB, vaginal bleeding; PRBC, packed red blood cells.


The majority of patients opted for expectant management (64.3%, n = 9), and the average GA at delivery was 28 weeks and 3 days (16 weeks and 6 days to 34 weeks and 5 days). One patient developed an early-onset HELLP-like syndrome at 16 weeks and 6 days, which prompted treatment with dilation and evacuation (D&E). Another patient experienced persistent vaginal bleeding throughout the pregnancy, resulting in preterm labor and vaginal delivery at 20 weeks and 2 days. A third patient developed hemorrhage and chorioamnionitis and was delivered at 17 weeks and 5 days. Two patients who opted for expectant management also had postpartum hemorrhage, with one of these requiring a hysterectomy due to bleeding after emergent delivery at 24 weeks and 5 days. She subsequently required treatment for metastatic GTN ([Table 3]).

None of the patients who opted for termination of pregnancy had complications from the procedure, including hemorrhage ([Table 3]). One of the patients who underwent termination of pregnancy developed pulmonary edema at 20 weeks 0 days at the time of diagnosis.

GTN was diagnosed in 28.6% of patients (n = 4), with two (2/8; 25%) from the expectant management group and two (2/5; 40%) from the termination group. The two cases of GTN from the termination group were International Federation of Gynecology and Obstetrics (FIGO) stages 1 and 3, while the two cases from the expectant management were FIGO stages 3 and 4. All were treated with intravenous (IV) methotrexate. One patient also received leucovorin, and the patient with FIGO stage 4 disease also received IV dactinomycin. Two of these patients were also noted to have a nadir in their hCG levels by day 56 postdelivery/evacuation.


#

Discussion

In this series, we analyzed the patient characteristics, diagnosis, pregnancy complications, and resultant obstetric outcomes of 14 pregnancies complicated by CHMCF. Complete hydatidiform moles (CHM) are generally homozygous 46, XX and result from duplication of the haploid genome of a single sperm following fertilization of an ovum in which the maternal chromosomes are lost during meiosis, or due to postzygotic diploidization in a triploid conception.[5] A multizygotic pregnancy consisting of a partial or complete HMCF is a rare complication of pregnancy, and the available cases series to date focus on GTN risk, instead of obstetrical risk.[6] A multicystic placental mass on ultrasound imaging is typically seen in the first trimester ([Figs. 1] [2] [3] [4] and [Supplementary Video S1]) and should trigger a referral to a maternal-fetal medicine specialist for further imaging and potential diagnostic testing. With improved ultrasound technology and rising rates of ART,[7] HMCF diagnoses may be made earlier and more frequently, highlighting the importance of data accrual on the course and outcome of these pregnancies.[8]

Zoom Image
Fig. 1 Dizygotic pregnancy with large complete hydatidiform molar tissue and normal placenta.
Zoom Image
Fig. 2 Dizygotic pregnancy at 11 weeks and 4 days with complete hydatidiform molar tissue and viable fetus.
Zoom Image
Fig. 3 Dizygotic pregnancy with complete hydatidiform molar tissue and abutting normal placenta from a viable fetus.
Zoom Image
Fig. 4 Trizygotic pregnancy at (A) 11 weeks and 5 days with complete hydatidiform molar tissue and at (B) 24 weeks with the head of twin B and complete hydatidiform molar tissue.

Supplementary Video S1 Dizygotic pregnancy with complete hydatidiform molar tissue and a viable fetus with normal placental tissue.


Quality:

The differential diagnosis of a multicystic placenta with a coexisting fetus can be broad, as a multicystic placenta can represent a hydropic abortus, chromosomal abnormalities, digynic triploid conceptions, PMD, or a molar pregnancy. These distinct diagnoses have varying complications, potential outcomes, and management strategies. The ability to differentiate between these diagnoses is key for optimal counseling and management. Pregnancies with these sonographic findings should be evaluated by and co-managed with a maternal-fetal medicine subspecialist. Maternal serum α-fetoprotein (MSAFP) measurements and β hCG measurements are helpful in confirming the diagnosis. The levels in our case series are comparable to previous case series with β hCG levels greater than 150,000 mIU/mL. Previous cases series have suggested a plateau of β hCG levels in the second trimester and that a failure to reach a plateau was associated with increased risk of adverse pregnancy outcomes.[7]

Ultrasound, β hCG, and MSAFP may not provide sufficient data to differentiate between possible diagnoses; thus, invasive diagnostic testing may be necessary for genetic analysis. Amniocentesis can be utilized to evaluate for a triploidy in the coexistent fetus or the placenta as this would be suggestive of a partial hydatidiform mole. Previous literature has suggested CVS of the suspected molar tissue as an alternative via molecular genotyping and segregation analysis of paternal and placental alleles, as absence of maternal alleles can confirm a diandrogenic complete mole.[9] [10] [11] Our series is the first to report common use of invasive testing in CHMCF, and to show that 40% of invasive procedures may yield no growth or insufficient sample in these cases. Preprocedural counseling regarding invasive testing should include this potential outcome of testing.

Furthermore, CHM is well recognized to have the potential for local invasion and distant spread. It has also been suggested that persistent trophoblastic disease and metastatic GTN are more pervasive with a multifetal gestation with concurrent mole, up to 30% increased risk.[12] β hCG and molar volumes have been used to predict malignant potential, although this is an area where more research is needed.[12]

The presence of a CHMCF creates complications for both the mother and the fetus with the clinical course frequently complicated by vaginal bleeding, preeclampsia, hyperemesis gravidarum, hyperthyroidism, and gestational trophoblastic disease.[10] Our case series describes the complication rates in a modern cohort, particularly highlighting the significance of morbid vaginal bleeding and hypertensive disorders of pregnancy in these women. A recent systemic review reported similar findings of a high rate of perinatal morbidities.[13]

Including the cases reported in this series, 16 reports of trizygotic pregnancy with two coexisting fetuses and a complete mole have been reported ([Table 4]).[5] [9] [10] [14] [15] [16] Of the 16 cases, 87.5% have been pregnancies conceived with ovulation induction medications. The clinical course of these pregnancies shows that vaginal bleeding is very common, presenting in 59% of the cases reported to date.

Table 4

Cases of trizygotic pregnancies consisting of complete mole and two co-existing twins

Study

Age (y)

Conception

GA at delivery (wk)

Maternal complications

Pregnancy outcome

GTD

Postpartum therapy

Confirmation of diagnosis

Sauerbrei et al[14]

23

Clomiphene

22

VB, PEC with severe features at 22 wk

Spontaneous abortion

No

MTX, ActD (5 cycles)

Postpartum by placental pathology and elevated hCG

Ohmichi et al[15]

34

hMG-hCG

17

VB

Spontaneous abortion

PTT

N/A

Postpartum by placental pathology and elevated hCG

Azuma et al[16]

24

hMG-hCG

19

VB

Spontaneous abortion

No

N/A

Postpartum by placental pathology

van de Geijn et al[24]

31

GIFT

24

VB

PTL, SVD, neonatal deaths of both twins

No

N/A

Antepartum US findings and elevated hCG

Confirmed postpartum

Shahabi et al[25]

25

Clomiphene

17

Hyperthyroidism, hyperemesis

Induced abortion due to hyperemesis

Choriocarcinoma, pulmonary metastasis

MTX (2 cycles)

Antepartum US findings and elevated hCG

Confirmed postpartum

Shozu et al[26]

31

IVF-ET

15

VB

Induced abortion due to VB

Invasive mole

MTX, ActD (6 cycles)

Postpartum by pathology and DNA polymorphisms in placental tissue

Higashino et al[27]

23

Clomiphene, hFSH-hCG

22

Hyperthyroidism, PEC with severe features, pulmonary edema

Induced abortion due to maternal status

Invasive mole

MTX (7 cycles), etoposide (2 cycles)

Antepartum US findings and elevated hCG

Confirmed postpartum

Gray-Henry et al[28]

31

Metrodin, hCG

16

Massive VB

Induced abortion due to life-threatening hemorrhage

No

N/A

Antepartum US findings and elevated hCG

Confirmed postpartum

Amr et al[29]

31

Clomiphene, hCG

30

None

PTL, SVD, neonatal death of 1 twin

No

N/A

Postpartum by placental pathology and elevated hCG

Rajesh et al[11]

29

Spontaneous

24

VB

PTL, SVD, neonatal death of both twins

No

N/A

Antepartum US findings and elevated hCG

Confirmed postpartum

Malhotra et al[12]

29

Spontaneous

21

VB

Spontaneous abortion

No

N/A

Antepartum US findings and elevated hCG

Confirmed postpartum

Takagi et al[30]

37

hMG, hCG

28

Cerclage placed

PTL, CD for malpresentation, survival of both twins

Invasive mole, pulmonary metastases

MTX (6 cycles)

Antepartum US findings and elevated hCG

Confirmed postpartum

Bovicelli et al[8]

32

ICSI

31

VB

Emergency CD for nonreassuring fetal testing, IUFD of one twin (fetomaternal hemorrhage)

No

N/A

Antepartum US findings and elevated hCG

CVS c/w all paternal genotype

Confirmed postpartum

Steigrad et al[31]

40

IVF

34

VB

CD due to VB, survival of both twins

Metastatic GTN, pulmonary metastases

MTX, FA (3 cycles)

Antepartum US findings and elevated hCG

Confirmed postpartum

Ko et al[32]

36

IVF-ET, donor embryo

33

PEC with severe features

CD due to PEC, survival of both twins

No

N/A

Antepartum US findings and elevated hCG

Confirmed postpartum

This study

30

GnTp, IUI

16

HELLP

SAB of twin B, then induced abortion of twin A due to maternal status

Metastatic GTN, pulmonary metastases

MTX

Antepartum US findings and elevated hCG

Confirmed postpartum (twin A unremarkable, twin B partial mole)

Abbreviations: ActD, actinomycin D; CD, cesarean delivery; EMA-CO, etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine; ET, embryo transfer; FA, folinic acid; GA, gestational age; GIFT, gamete intrafallopian transfer; GTD, gestational trophoblastic disease; GTN, gestational trophoblastic neoplasia; hCG, human chorionic gonadotropin; HEELP, hemolysis elevated liver enzymes low platelets syndrome; hFSH, human follicle stimulating hormone; hMG, human menopausal gonadotropin; ICSI, intracytoplasmic spermatic injection; IUFD, intrauterine fetal demise; IUI, intrauterine injection; IVF, in vitro fertilization; MTX, methotrexate; PEC, preeclampsia; PT, preterm; PTL, preterm labor; SAB, spontaneous abortion; SVD, spontaneous vaginal delivery; VB, vaginal bleeding.


The risk of GTN is higher in the presence of a complete mole compared with a partial mole (14–20% compared with 1–5%).[5] GTN can include invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. The series reported here suggests that the incidence of GTN may be higher in CHMCF than in other molar pregnancies, with 28.6% of patients in this series having GTN. Although the group who opted for termination had a high percentage of GTN, the FIGO stages appeared to be lower. This highlights the importance of counseling regarding the risk of distant metastatic disease with expectant management and need for close patient follow-up postdelivery of patients with CHMCF.

A recent meta-analysis by Albright et al states that the risk of GTN in patients with normalization of β HCG by day 56, or after 8 weeks, is 0.35% for complete mole and 0.03% for partial mole.[17] This is in contrast to our series, where 50% of CHMCF patients who developed GTN had a nadir of β hCG by day 56. More studies and collaborative efforts are warranted to further evaluate the possibility of additional risk of GTN. It is well known that CHMCF carries a much greater risk of pregnancy complication if expectant management is performed, with increased risk of vaginal bleeding, preeclampsia, and preterm labor, but the increased risk of CHMCF may also carry a significantly increased risk of GTN, and this may indicate a longer period of serial β hCG measurements and surveillance and should prompt extensive patient counseling.[1] [3] [4]

One of the greatest strengths of our study is that this is the largest series to date for obstetric data in CHMCF and includes a wide geographic region. Additionally, the use of social media to engage physicians from across the country is a novel approach to transmural collaborations, instead of individual reports of complex cases. Once connected, the physicians were able to use a standardized collection of data across institutions, giving more uniformity to the data for comparison. Although our study has many strengths, it is limited by the potential of selection bias, and given its retrospective recall of cases, the worst cases with the poorest outcomes could have been collected and reviewed. Furthermore, the observational nature of the study cannot truly compare the management protocols, as is often the case with rare disorders.


#

Conclusion

Overall, our findings demonstrate that it is possible to manage CHMCF expectantly but requires shared decision-making while factoring in maternal antepartum and peripartum risks, as well as increased risk of subsequent metastatic GTN. This case series can serve as a tool for engaging in full counseling of patients about the varied and potentially significant outcomes of CHMCF gestations, which are likely to be on the rise with the increasing use of ART.

Additionally, it is also important to consider innovative methods of extramural collaboration to amplify data accrual for rare disorders, such as CHMCF. This case series demonstrates a novel collaboration, as the idea was initiated in a private social media group of physicians and resulted in a wide collaborative effort from institutions across the United States. These same methods can be used with other rare complications to expand our knowledge base and lead to more meaningful observations from which to draw conclusions.


#
#

Conflict of Interest

None declared.


Address for correspondence

Roxanna A. Irani, MD, PhD
Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
550 16th Street, 7th floor, Box 0132, San Francisco, CA, 94143

Publication History

Received: 20 October 2020

Accepted: 08 October 2021

Accepted Manuscript online:
25 October 2021

Article published online:
14 February 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA


Zoom Image
Fig. 1 Dizygotic pregnancy with large complete hydatidiform molar tissue and normal placenta.
Zoom Image
Fig. 2 Dizygotic pregnancy at 11 weeks and 4 days with complete hydatidiform molar tissue and viable fetus.
Zoom Image
Fig. 3 Dizygotic pregnancy with complete hydatidiform molar tissue and abutting normal placenta from a viable fetus.
Zoom Image
Fig. 4 Trizygotic pregnancy at (A) 11 weeks and 5 days with complete hydatidiform molar tissue and at (B) 24 weeks with the head of twin B and complete hydatidiform molar tissue.