CASE STUDY-MOLAR PREGNACY

INTRODUCTION
First-trimester pregnancy is defined as the first 12 weeks after the patient’s last
menstrual period. It is the period of human development associated with the highest
complication rate. During this critical period, ultrasound may be used to confirm
intrauterine pregnancy, determine viability, and exclude ectopic pregnancy or
gestational trophoblastic disease (GTD).

A molar pregnancy also known as hydatidiform mole is a rare complication of

pregnancy characterized by the abnormal growth of trophoblasts, the cells that
normally develop into the placenta. Molar pregnancy (molahydatidosa) belongs to a
group of diseases classified as gestational trophoblastic disease resulting from
abnormal fertilization (Dr. Gupta, A. et al. 2019). It is divided into two types -
complete and partial molar pregnancy, based on distinctive histopathological features
and genetic abnormalities. GTD includes a spectrum of tumours that can be benign or
malignant. Benign entities include complete and partial moles.

A complete mole may be seen as an intrauterine mass with cystic spaces without any
associated foetal parts. In comparison, a partial mole may be visualized as a
gestational sac containing amorphous echoes representing foetal parts with an
enlarged cystic placenta. Pathogenetically, it is a complete or partial trophoblastic
proliferation (of cyto- and syncytiotrophoblasts) with hydropic degeneration of the
placental villi.

Complete molar pregnancy usually occurs when an egg without maternal

chromosomes is fertilized by a single sperm, with a subsequent duplication of its
DNA, resulting in a 46, XX paternal karyotype. Abnormal fertility is associated with a
maternal autonomic recessive mutation, most commonly NLRP7 on chromosome
19q, leading to recurrent molar pregnancies. As a result, hydropic trophoblastic
degeneration and lack of embryonic structures develop (Hancock, B. W. and Tidy, J.
A. 2002).
According to Malhotra, N. et al. (2002); partial mole is a result of fertilization of a
haploid normal oocyte with two spermatozoa simultaneously, with the formation of a
zygote with a triploid set of chromosomes (69 XXX, 69XXY or 69 XYY) and is most
often associated with the development of an irregularly shaped foetus. A possible
variant is also a partial hydropic degeneration of the placenta resulting in a foetus with
a diploid chromosome set. Not infrequently, partial molar pregnancy remains
undiagnosed in cases with first trimester pregnancy loss in the form of incomplete or
missed abortion. Medical literature report that in less than 25% of cases, partial mole
occurs with the development of an euploid viable foetus, with the following options
possible: most often it is a twin pregnancy, with one gestational sac containing normal
foetus with normal placenta and the other one with a complete molar pregnancy; the
second type is a twin pregnancy with one of the foetuses being normal with a normal
placenta and the other sac having an incomplete mole.

A molar pregnancy can have serious complications including a rare form of cancer
and requires early treatment. The majority of complete moles present with vaginal
bleeding and markedly elevated beta-human chorionic gonadotropin (b-hCG) values.
A molar pregnancy may seem like a normal pregnancy at first, but most molar
pregnancies cause specific signs and symptoms, including: dark brown to bright red
vaginal bleeding during the first trimester, severe nausea and vomiting, sometimes
vaginal passage of grape-like cysts, pelvic pressure or pain. Other signs are rapid
uterine growth where the uterus is too large for the stage of pregnancy, high blood
pressure, pre-eclampsia- a condition that causes high blood pressure and protein in the
urine after 20 weeks of pregnancy, ovarian cysts, anaemia and over-active thyroid
(hyperthyroidism).

Case Presentation: A 28 years old black African lady of unknown LMP, Para 2
Gravida 3 with positive pregnancy test done a week prior to her visit presented to the
Radiology Department complaining of vaginal bleeding and history of treated vaginal
discharge, nausea, vomiting and abdominal fullness. On physical examination, she
was anaemic, with raised BP, and relatively unstable. The physical pelvic exam had
revealed a small amount of dark blood without signs of active bleeding, an anteverted
uterus of eight weeks size and a closed cervix. She had no laboratory results of
quantitative beta-human chorionic gonadotropin levels and was referred by a General
Practitioner for ultrasound of the pelvis to rule out miscarriage.

INDICATION
 First trimester obstetric scan to rule out early pregnancy miscarriage.

Date Of Examination: 15 August 2022

PATIENT INFORMATION

Date of Birth: 16 December 1994

Parity: 2
Gravida: 3
LMP: Unknown
Contraception: Nil
Marital status: Single
Sex: Female
Level of Education: Ordinary Level

EQUIPMENT
Mindray DC-6 Ultrasound machine.
3.5-5MHz curvilinear probe .
Sony High glossy thermal paper.
Ultrasound gel.
Sony Ultrasound Printer.

PATIENT PREPARATION, PATIENT CARE AND PROTOCOL

Standard First Trimester Obstetric Transabdominal Scan Protocol documented in
appendix B attached.
OBSERVATIONS AND FINDINGS
 The uterus was bulky, anteverted, non- gravid(with no visible GS) and non
fibroid and bulky measuring 9.34 cm x 7.55 cm x 8.20 cm with a heterogeneous
echotexture.
 A predominantly solid, large central heterogeneous echogenic mass that expands
the endometrial canal with multiple solid cystic spaces and no identifiable foetal
parts or gestational sac was seen occupying the entire bulky uterus.
 The intrauterine mass contained multiple cystic spaces of varying sizes from 0.6
to 0.8 cm and it demonstrated a snowstorm appearance with both peripheral and
intra-mass vascularity on color Doppler.
 Pulsed wave Doppler of a peripheral artery demonstrated high velocity of 28.61
cm/s.
 A left ovarian unilocular hypoechoic complex cystic mass measuring 3.13 cm in
the short axis and 1.75cm in long axis was seen. The cystic ovarian mass
demonstrated posterior enhancement and peripheral vascularity on color Doppler
interrogation. The right ovary appeared normal in size and echogenicity.
 The urinary bladder was partial distended hence it was not assessed.
 No evidence of pelvic free fluid, or any free fluid collections seen in the POD.
 No evidence of ectopic pregnancy seen sonographically.

COMMENT
 A predominantly solid, large central heterogeneous echogenic intrauterine mass
that expands the endometrial canal with innumerable uniformly distributed cystic
spaces and no identifiable foetal parts or gestational sac is highly suggestive of
complete molar pregnancy/ hydatidiform mole.
 A left ovarian unilocular hypoechoic complex cystic mass measuring 3.13 cm in
the short axis and 1.75cm in long axis is highly suggestive of left ovarian theca
luteal cyst.
 No evidence of PID / ectopic pregnancy shown by ultrasound.
 Recommend laboratory tests of quantitative beta-human chorionic
gonadotropin levels and a CT scan /PET scan to stage the disease.
 Rescan after seven days with laboratory results of quantitative beta-human
chorionic gonadotropin levels.
 Differential Diagnosis is of Abnormal villous morphology; or Early abortus with
trophoblastic hyperplasia; or Hydropic abortus.
 Clinical correlation highly advised.
Signed………………………………….S. TANGWADZANA
(Diagnostic Radiographer/Student Sonographer)
DISCUSSION
Pathophysiology
A molar pregnancy is a rare complication of pregnancy characterized by the abnormal
growth of trophoblasts, the cells that normally develop into the placenta. In Europe,
North and South America, (Kubelka-Sabit, K.B., et al., (2017); reported that
hydatidiform moles observed in approximately 1 in every 1,000 pregnancies are
diagnosed as a molar pregnancy and the prevalence is 5 to 15 fold higher in East Asia.

In a complete molar pregnancy, an empty egg is fertilized by one or two sperm, and
all of the genetic material is from the father. In this situation, the chromosomes from
the mother's ovum are lost or inactivated and the father's chromosomes are duplicated,
thus, only paternal DNA is expressed. This most often occurs when two sperms
fertilise an egg/ovum, resulting in an extra copy of the father's genetic material
(Lurain, J. R. 2010). The karyotype of complete moles is usually 46,XX 90% of the
time and 46,XY 10% of the time; the chromosomes derived completely from the
father as a complete mole likely results from the fertilization of anuclear empty ovum
by a haploid sperm that duplicates its own chromosomes after meiosis.

On the other hand, in partial moles, the karyotype is 90% of the time triploid and
either 69,XXX or 69,XXY. This karyotype arises when a normal sperm subsequently
fertilizes a haploid ovum duplicates and or when two sperms fertilize a haploid ovum.
In partial moles, both maternal and paternal DNA is expressed.

Histopathology
 Hydatidiform mole is characterized by an overgrown villous trophoblast with
cystic "swollen" villi which macroscopically can be visible in the
second trimester, as clusters of vesicles (similar to small grapes) developed from
the transformation of chorionic villi. Complete mole differs from partial mole, in
cytogenetic and microscopical appearance. Important is a complete lack of
embryonic/foetal tissue in complete moles and the presence of embryonic tissue
in partial moles.
 Microscopically, a complete mole has markedly hydropic and deformed chorionic
villi with the formation of "cisterns" containing stromal fluid; there is a
peripheral proliferation of both cytotrophoblast and syncytiotrophoblast, arranged
 in lace-like structures, papillary formation, or circumferential. In normal early
placenta the cytotrophoblast and syncytiotrophoblast are polarized. There is the
absence of foetal stromal blood vessels. An immature vascular network is
otherwise present, positive for CD31, with dysmorphic features such as a
complete lack of lumen.
 In partial mole, there are hydropic chorionic villi surrounded by hyperplastic
trophoblasts with variable degrees of central cistern formation, with an irregular
maze-like pattern; also, there are normal chorionic villi and embryonic or foetal
tissue mixed with hydropic villi. There are recognizable foetal blood
vessels containing foetal red blood cells. The curettage material should be
examined carefully, especially in first trimester pregnancies, and if a partial mole
is suspected the whole specimen should be examined.
 The main differential diagnosis is with a hydropic abortion, where the main clue
is the presence of villous oedema only with microscopical evaluation and lacks
cistern formation or trophoblastic proliferation.
 A pitfall in hydropic abortion is the presence of polar stratification of anchoring
trophoblast in a first-trimester placenta. The villous size in hydropic abortion
ranges from small, to medium and large.
 An important marker that aids in the diagnosis of the complete mole is the
presence or absence of p57 in immunohistochemistry. This marker is a paternal-
imprint inhibitor gene so its expression implies the maternal contribution; in
brief, the absence of p57 expression supports the diagnosis of androgenetic
gestational disease with complete mole (Xing, D. et al. 2021). Moles also
express p53, p21, cyclin E, and MCM7.

ULTRASOUND FEATURES OF MOLAR PREGNANCY

 In a complete mole, the ultrasound findings include a heterogeneous mass in the
uterine cavity with multiple anechoic spaces, most commonly referred to as a
"snowstorm" appearance. These small cystic areas are typically the hydropic villi
described previously in the histopathology section. Furthermore, there is the
absence of an embryo or foetus, and no amniotic fluid is present.
 In a partial mole, there typically is the finding of a foetus which may be viable,
the presence of amniotic fluid, and the placenta appears to have enlarged, cystic
spaces (often described as "Swiss cheese" appearance). In one study, it was noted
 that partial moles were diagnosed as a missed or incomplete abortion in 15% to
60% of cases. 
NB: If a molar pregnancy is diagnosed, the next step is typically a CT scan and PET
scan to stage the disease. Furthermore, a chest x-ray should be obtained if the
patient's initial symptoms included any signs of respiratory distress or increased
breathing to evaluate for pulmonary oedema.

Patient Presentation
The case presentation of a 28 year old pregnant black African woman with complete
molar pregnancy after ultrasound scan, a history of unknown LMP, Para 2 Gravida 3
with positive pregnancy test done a week prior to her visit; complaining of vaginal
bleeding and history of treated vaginal discharge, nausea, vomiting and abdominal
fullness. On physical examination, she was anaemic, with raised BP, and relatively
unstable. The physical pelvic exam had revealed a small amount of dark blood
without signs of active bleeding, an anteverted uterus of eight weeks size and a closed
cervix. She had no laboratory results of quantitative beta-human chorionic
gonadotropin levels.

Transabdominal ultrasound revealed an anteverted, non- gravid(with no visible GS)

and non fibroid and bulky measuring 9.34 cm x 7.55 cm x 8.20 cm with a
heterogeneous echotexture. A predominantly solid, large central heterogeneous
echogenic mass that expands the endometrial canal with multiple solid cystic spaces
and no identifiable foetal parts or gestational sac was seen occupying the entire bulky
uterus. The mass contained multiple cystic spaces of varying sizes from 0.6 to 0.8 cm.
The mass demonstrated a snowstorm appearance with both peripheral and intra-mass
vascularity on color Doppler. Pulsed wave Doppler of a peripheral artery
demonstrated high velocity of 28.61 cm/s. A left ovarian unilocular hypoechoic
complex cystic mass measuring 3.13 cm in the short axis and 1.75cm in long axis was
seen. The theca leuteal cyst demonstrated posterior enhancement and peripheral
vascularity on color Doppler interrogation.

Case Discussion:
 A significant risk factor for the development of complete molar pregnancy is the
age of the mother. Compared with the risk in women aged 21 to 35 years, the risk
 is 1.9 times higher for women 35 years, and 7.5 times higher for women>40
years, including 1 in 3 pregnancies for women>50 years (MOJ Anat Physiol.
2020;7(5):150‒153).
 The transabdominal ultrasound findings obtained are consistent with what is
documented in medical and reviewed literature above. However, such a
dependence is not established with regard to the risk of developing a partial mole.
Partial molar pregnancy is more common in women with a history of irregular
menstruation, miscarriage and oral contraceptives for more than 4 years, while
ethnicity, dietary factors and ovulation induction are not associated with an
increased risk.
 Complete molar pregnancy is most often presented by vaginal bleeding at 6 - 16
weeks of gestation in 90% of cases. Other classic symptoms, such as higher than
expected gestational age, hyperemesis, hyperthyroidism and trophoblastic
embolization are less common in the first trimester and in recent years due to
earlier diagnosis, as a result of the widespread use of high-quality/resolution
ultrasonography and quantitative measurement of human chorionic gonadotropin
(hCG). Complete molar pregnancy is also associated with a similar clinical
manifestation.
 In addition to the typical clinical manifestation as a result of excessive hCG
production, molar pregnancy is characterized by a specific ultrasound features.
These typical ultrasound manifestations of a complete molar pregnancy include
the visualization of a diffuse, multi-cystic and often hyper-vascular intrauterine
mass (“snowstorm” or “honeycomb” type) with no foetal tissues. Partial molar
pregnancy may present as a localized placental abnormality with a living embryo,
spontaneous intrauterine foetal death, or the presence of an empty gestational sac
(blighted ovum).
 Some authors propose the following ultrasound criteria for specific findings of
partial molar pregnancy as a ratio of transverse to Antero-posterior diameter of
the gestational sac >1.5 and cystic changes in the placenta and/or irregularity of
the contour of the decidua, placenta or myometrium (Kirk, E. 2007).
 During the first trimester, the frequency of diagnosing a complete mole is higher
than that of a partial mole, increasing with advancing of gestational age. Fowler
D. J., et al. (2006); analysed 378 ultrasound-proven molar pregnancies,
demonstrating the accuracy of the ultrasound diagnosis in 200 of 253 (79%)
 complete hydatidiform moles and 178 of 616 (29%) partial hydatidiform
pregnancies.
 Several factors determine the prognosis of a foetus in a partial molar pregnancy,
such as the karyotype of the foetus, the size of the area with hydropic
degeneration of the placenta, the rate of hydropic degeneration and the
manifestation of foetal anaemia or other obstetric complications such as pre-
eclampsia, thyrotoxicosis and vaginal bleeding.
 According to Hsieh, C. C., et al. (1999); in singleton pregnancies with dizygotic
normal foetus with partial molar placenta, pregnancy development depends on the
genesis of placental degeneration, from amniotic diploidy to chorionic villus
triploidy, which determines two different types of placental pathology: focal and
diffuse partial degeneration. In most cases, however, the diagnosis of a partial
mole is in the case of intrauterine foetal death.
 Despite early diagnosis of complete mole, which leads to fewer complications, no
concomitant reduction in the incidence of post-molar gestational trophoblastic
neoplasia (GTN) has been observed [Fowler D. J., et al. (2006)]; approximates
that 10% to 20% of women with a complete molar pregnancy and 0.5% to 11%
with a partial molar pregnancy will continue to develop persistent, invasive
gestational trophoblastic disease, including invasive mole, choriocarcinoma, or
placental trophoblastic tumour.
 In case of a suspected diagnosis of molar pregnancy on the basis of medical
history, physical examination, hCG level and ultrasound findings, the physician
should assess the presence of medical complications (anaemia, pre-eclampsia,
hyperthyroidism) which have to be treated.
 Key diagnostic and laboratory tests include: complete blood count, complete
metabolic panel, thyroid function test, urine test, chest x-ray, an
electrocardiogram, coagulation status and blood group with rhesus factor.
The case under discussion therefore was positive for the ultrasound and clinical
presentation of complete molar pregnancy diagnosed in the first trimester.

MANAGEMENT
Patients who are diagnosed with molar pregnancy must be evaluated for possible
complications such as: Over-active thyroid, anaemia, and toxaemia of pregnancy.
Patients should have a complete examination and laboratory testing [Lurain, J. R.
(2010)]. After any medical complications have been addressed, a decision must be
made concerning the best method of evacuation.

Suction curettage is the optimal method of evacuation, regardless of uterine size, in

patients who wish to retain reproductive function, because it carries a significantly
lower risk of excessive bleeding, infection, and retained molar tissue than methods
involving induction with oxytocin or prostaglandin. Rh immune globulin should be
given to patient with RH conflict.

Maximum dilatation of the cervical canal and aspiration with a 12- to 14-millimeter
cannula under ultrasound control are recommended. As the risk of excessive bleeding
increases with the size of the uterus, it is necessary to provide at least two sacks of
blood preoperative in cases with uterine size >16 gestational weeks.

Hysterectomy is an alternative in patients who do not wish to maintain fertility or who

are at increased risk of developing post-molar gestational trophoblastic disease.
Adnexa can be preserved bilaterally, even in the presence of theca-lutein cysts. In
addition to the evacuation of molar pregnancy, hysterectomy provides permanent
sterilization and eliminates the risk of local myometrial invasion as a cause of
persistent mole. Due to the possibility of metastasis even after hysterectomy, the risk
of post-molar gestational trophoblastic disease still remains between 3% and 5%, thus
requiring long term follow-up of hCG [Lurain, J. R., (2011)].

Drug induction and hysterectomy as proposed by Ngan, H. Y. S., et al. (2003); are
not recommended for termination of molar pregnancy. These methods increase
maternal morbidity, such as excessive blood loss, incomplete evacuation requiring
curettage and the need for cesarean delivery in subsequent pregnancies. Prophylactic
chemotherapy during or immediately after evacuation of molar pregnancy is
associated with a reduction in the incidence of persistent mole from approximately
20% to 3%. Chemotherapy is recommended in high-risk patients (age>40 years,
hCG>100,000 mIU/mL, uterine enlargement, theca luteal cysts >6 cm, medical
complications) and/or when adequate hCG monitoring is not possible.
After termination of molar pregnancy, follow-up is essential for the detection of
trophoblastic disease (invasive mole or choriocarcinoma), which develops in
approximately 15% to 20% of patients with a complete mole and 1% to 5% in a
partial mole. Clinically uterine involution, regression of theca-lutein cysts and
cessation of vaginal bleeding are good prognostic signs.

In addition, final follow-up requires serial measurements of serum hCG every 1 to 2

weeks, until three consecutive tests establish normal hCG levels. hCG monitoring
should be determined at 3-month intervals for 6 months after documented negative
values. Contraception is recommended during the follow-up period of 6 months after
the first normal hCG result. Oral contraceptives are preferred because they have the
advantage of suppressing endogenous luteinizing hormone (LH), which may interfere
with the measurement of hCG at low levels.

Indications for treatment of post-molar disease are: plateau of hCG levels within
testing every week for 3 weeks, increase in hCG levels ≥10% with weekly
measurement for 2 weeks, persistently elevated hCG levels 6 months after evacuation,
histopathological diagnosis of choriocarcinoma or trophoblastic tumour or evidence
of metastasis. In all subsequent pregnancies, pathological examination of the placenta
or other products of conception is recommended, as well as monitoring of the hCG
level 6 weeks after birth.
NB: Patients are monitored to prevent the recurrence of benign moles and the
development of malignant neoplasia, which can metastasise to the brain, liver or
lungs. Chest x-rays and the analysis of HCG levels for six months to one year are
necessary]. Recurring moles are treated with methotrexate, a low-level chemotherapy
[Sebire, N. J., and Seckl, M. J. (2008)].

The American College of Obstetricians and Gynaecologists has recommended that

after evacuation of a mole, serum HCG levels should be monitored every 1-2 weeks
in all patients while the levels are elevated and then at monthly intervals for an
additional 6 months once the levels become undetectable (5MIU per millilitre).
 The in this case study was not followed up for management however, she was
recommended for further diagnostic and laboratory tests.
CONCLUSION

While histological diagnosis remains the gold standard for diagnosis, positive
ultrasound features should raise the index of suspicion in cases where the diagnosis is
doubtful. While histological diagnosis remains the gold standard for diagnosis,
positive ultrasound features should raise the index of suspicion in cases where the
diagnosis is doubtful.
In the first few months of pregnancy, molar pregnancy is associated with a higher
incidence of vaginal bleeding or discharge, abdominal pain and morning sickness.
However, as these symptoms are relatively non-specific, they rarely lead to the
diagnosis being made prior to the routine first ultrasound scan.
In complete molar pregnancy, the ultrasound characteristically shows an absent
gestational sac and a complex echogenic intrauterine mass with cystic spaces.
Complete molar pregnancy is associated with marked cystic changes and mass
formation and is often diagnosed ultrasonographically. However, correct prospective
diagnosis was made more frequently in this study than in older reports, perhaps due to
improved spatial resolution of ultrasonographic equipment.
REFERENCE

1. Fowler, D. J., Lindsay, I. and Seckl, M. J. (2006). Routine pre-evacuation

ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from
a regional referral center. Ultrasound Obstet Gynecol. 2006;27(1):56–60.
2. Hancock, B. W. and Tidy, J. A. (2002). Current management of molar
pregnancy. J Reprod Med. 2002;47(5):347–354.
3. Hsieh, C. C., Hsieh, T. T. and Hsueh, C. (1999). Delivery of a severely
anaemic foetus after partial molar pregnancy; clinical and ultrasonographic finding.
Hum Repord. 1999;14(4):1122–1126.
4. Kirk, E., Papageorghiou, A. T. and Condous, G. (2007). The accuracy of first
trimester ultrasound in the diagnosis of hydatidiform mole. Ultrasound Obstet
Gynecol. 2007;29(1):70–75.
5. Kubelka-Sabit, K. B. (2017). Molecular and Immunohistochemical
Characteristics of Complete Hydatidiform Moles. Balkan journal of medical genetics :
BJMG, 2017. 20(1): p. 27-34.
6. Lurain, J. R. (2010). Gestational Trophoblastic Disease I: Epidemiology,
Pathology, Clinical Presentation And Diagnosis Of Gestational Trophoblastic
Disease, And Management Of Hydatidiform Mole. Am J Obstet Gynecol 203: 531-
539. [Crossref]
7. Lurain, J. R., (2011). Gestational Trophoblastic Disease. Ii: Classification And
Management Of Gestational Trophoblastic Neoplasia. Am J Obstet Gynecol.
2011;204(1):11–18.
8. Malhotra, N., Deka, D. and Takkar, D. ()2001). Hydatidiform Mole With
Coexisting Live Foetus In Dichorionic Twin Gestation. Eur J Obstet Gynecol Reprod
Biol. 2001;94(2):301–303.
9. Ngan, H. Y. S., Bender, H., and Benedet, J. L., (2003). Gestational
Trophoblastic Neoplasia, Figo 2000 Staging And Classification. Int J Gynecol Obstet.
2003;83:175–177.
10. Sebire, N. J., & Seckl, M. J. (2008). Gestational Trophoblastic Disease:
Current Management Of Hydatidiform Mole. British Medical Journal, 337 (aug15 1),
453-458. doi:10.1136/bmj.a1193
11. NCCN Guidelines: gestational trophoblastic neoplasia. version 1. 2019, 2018.