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Introduction
A hydatidiform mole is a disease that occurs due to abnormal proliferation of the trophoblastic epithelium and placental villous oedema, included in the spectrum of gestational trophoblastic diseases (GTD).1 2 It is usually benign but can become malignant, invasive and metastatic.1 3
This disease is classified as partial hydatidiform mole (PHM) or complete hydatidiform mole (CHM). CHM occurs in approximately 1 to 3 per 1000 pregnancies.1 3 In rarer cases, a viable fetus can develop with a coexisting complete mole (CHMCF), occurring in every 1/20 000 to 1/100 000 pregnancies.2–8 Its incidence is increasing due to the rise of artificial fertilisation.4 5 GTD is prone to maternal and fetal complications, such as pre-eclampsia, vaginal bleeding, hyperthyroidism and fetal malformations.3 4 8 Due to the risk of malignancy, pregnancy interruption might be recommended.2–4 9 10
The coexistence of a viable fetus with a mole distinguishes it into three types. Initially, the primary category arises within the context of twin pregnancies, wherein a single fetus possesses a diploid karyotype, comprising 23 maternal and 23 paternal chromosomes and exhibit a morphologically normal placenta, which is concurrently correlated with a CHM (46 paternal chromosomes). The second type is equivalent to a triploid fetus (23 maternal and 46 paternal chromosomes). The third type is a twin pregnancy, consisting of a fetus with a diploid karyotype (23 maternal and 23 paternal chromosomes) with a normal placenta and another fetus with a triploid karyotype (23 maternal and 46 paternal chromosomes) associated with a PHM.1 2 6 8 9
It is essential to differentiate CHM and PHM due to the morbidity and mortality.1 6 CHM has a higher risk of developing choriocarcinoma and progressing with metastasis.1 6 8 10 The distinction is made by histopathological examination.3 4
Knowledge is limited regarding the management and outcomes of CHM associated with a viable fetus.3 8 In most cases, intrauterine fetal death, abortion and pregnancy termination occur due to the risks involved.2 3 5 10
This case report, approved by the Ethics Committee (protocol 6.741.820) online supplemental file 1, describes a patient with a twin pregnancy formed by a CHM with a viable fetus. The decision was made, together with the patient, to adopt conservative management.
Supplemental material
Once the case was described, a literature review was performed through the databases PubMed, Virtual Health Library (VHL) and Medline. The research was done between April and December 2023, with the descriptors ‘hydatidiform’ AND ‘complete’ AND ‘mole’ AND ‘coexisting’ AND ‘fetus’. The articles included were published no later than 10 years ago; they were published in English; they consisted of case reports, case series and literature reviews of CHMCF. The authors excluded editorial reviews, articles published more than 10 years ago, those involving PHM, and those not addressing CHMCF. Three reviewers (JPdO, JBM and JEK) independently screened articles in PubMed, VHL and Medline. In the event of discrepancies, a fourth reviewer (GW) adjudicated the selection using the predefined exclusion and inclusion criteria. After the perusal of the studies, 10 were deemed eligible and are accordingly included in this review.
Case report
The patient was 29-year old and was unsuccessfully trying to conceive for 18 months. She had a history of polycystic ovary syndrome, antiphospholipid antibody syndrome and spontaneous abortion. A hysterosalpingography was performed to investigate infertility, which showed bilateral tubal occlusion; it was later corrected video laparoscopically. Subsequently, ovulation was evaluated two months post the initial assessment via transvaginal ultrasound (TVUS), revealing the absence of follicular development.
The next step consisted of scheduled intercourse combined with ovulation induction. The patient returned with beta-human chorionic gonadotropin (β-hCG) at 2 712.3 mIU/mL. TVUS showed two gestational sacs. One month later, the β-hCG level was 216 259 mUI/mL.
The first-trimester morphological ultrasound was performed at a gestational age (GA) of 13+4 (figure 1A). It described a ‘heterogeneous mass, with slight vascularisation on Doppler, measuring 145.1 cm³, suggestive of previous total trophoblastic degeneration’. The fetus had a normal fetal heartbeat and morphology. The report suggested placental mesenchymal dysplasia or hydatidiform mole.
Ultrasound, gross specimen and immunohistochemistry. (A) First-trimester morphological ultrasound. (B) Ultrasound at 16 weeks and 1 day. (C) Postoperative image of the hydatidiform mole. (D) Immunohistochemically stained images of the hydatidiform mole.
The following ultrasounds showed a fetus weighing 149 g with a GA of 16+1 (figure 1B). At GA 23+3, the morphological ultrasound evidenced a fetus in the 22nd percentile and a mass. Furthermore, laboratory tests showed transient hyperthyroidism and gestational diabetes mellitus. The patient’s blood pressure increased after 22 weeks. However, there was no indication of pre-eclampsia.
The gestation interruption was made at GA 31+6 after the ultrasound showed an intrauterine growth restriction (IUGR) associated with oligohydramnios. Considering potential risks, a caesarean delivery was scheduled for the subsequent day. The procedure was unremarkable and the fetus had Appearance, pulse, grimace, activity, and respiration (APGAR) score of 9 and 10. The infant weighed 1535 g and measured 35 cm in length. Successfully, the hydatidiform mole was removed (figure 1C).
The mole was monitored after the delivery through measurement of β-hCG and TVUS. β-hCG levels gradually decreased; 5 months after delivery, it was <2. TVUS showed a normal pelvis.
Postsurgical removal immunohistochemical analysis of the placenta tumour tissue revealed a negative staining result for p57 (figure 1D). The report concluded with ‘Histological image and immunohistochemical profile compatible with CHM’, confirming the diagnosis.
Discussion
The patient was identified to have three risk factors associated with GTD: blood type A, previous abortion and artificial fertilisation.1 5 Studies have shown that one-third of people who develop moles have undergone ovulation induction.3
Ultrasound is the main diagnosis method for this disease and placental abnormalities are best visualised between gestational weeks 12–14.4 6 9 10 The images may show a ‘bunch of grapes’ and a ‘snowstorm’, which are characteristic of hydatidiform mole.4 5 7–10 This was visualised in the ultrasound performed at this patient’s GA 13, along with a placenta and a live fetus without anomalies, leading to the identification of a coexistent mole.
Nevertheless, the extant literature delineates the challenges inherent in diagnosing GTD. An anatomopathological examination of the placenta afterbirth or amniocentesis is recommended to confirm the hypothesis.3 4 10 In this case, the diagnosis of CHM was confirmed through immunohistochemical examination afterbirth.
The morbidity of the disease is related to complications, with maternal-related obstacles such as haemorrhage, pre-eclampsia and hyperthyroidism.2–5 7 8 10 Fetus-related complications are IUGR, prematurity and death.2 4 Literature findings suggest predictive factors for fetal survival, like initial β-hCG levels <4 00 000 mIU/mL and absence of clinical conditions (pregnancy-induced hypertension, hyperthyroidism, hyperemesis gravidarum).3 Therefore, continuation of a pregnancy with a viable fetus and CHM in two different gestational sacs is rare.2 3 10 In this case, the patient developed hypertension during her pregnancy but did not develop preeclampsia; she also presented transient hyperthyroidism.
Due to the high morbidity of the disease, the predominant course of action reported is to terminate the pregnancy, which contributes to the scarcity of publications with guidance regarding the appropriate management of these cases.3 4 7 10 In recent years, successful cases of pregnancies with coexisting moles have been reported, suggesting that complications can be managed.3 Furthermore, reports show that the risk of malignancy does not increase with GA.3 5 6 10 The success rate is around 40%.10
Moreover, the risk of developing persistent gestational trophoblastic neoplasia after childbirth is higher than in cases of a single mole. Yet, interrupting the pregnancy does not reduce this risk, showing that expectant management is an option.3 5 10 Thus, the decision in the present case was to continue the pregnancy with close monitoring of the patient and potential complications.
It is possible to deliver at term depending on maternal comorbidities, fetal vitality and quality of monitoring, although 70% are preterm pregnancies.2 4–8 10 In the present case, the pregnancy was terminated at GA 31+6 due to fetal distress evidenced by IUGR and oligohydramnios. Despite these conditions, the fetus was born without complications.
Postpartum follow-up is essential due to the risk of malignancy.1 3 6 8 10 CHM are frequently more invasive than PHM, ranging from 7% to 17%, and they have a higher risk of malignancy.1 Hence, β-HCG should be measured until negative.3 10 The patient had a 6-month follow-up with β-hCG and TVUS, which showed a gradual decrease in the hormone and no indications of disease.
Finally, we emphasise the importance of this report. Contrary to the study mentioned, the outcome was a healthy fetus, and there was no need to interrupt the pregnancy at a non-viable stage.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by Ethics Committee of Pontifical Catholic University of Parana—number 6.741.820. Participants gave informed consent to participate in the study before taking part.
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Collaborators JPdO, JBdM and JEK drafted, designed, planned, organised and interpreted the data analysis and manuscript writing. GW contributed to the conception and conducted the work, drafted the data analysis and reviewed it critically. All the authors approved the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Contributors JPdO, JBdM and JEK drafted, designed, planned, organised and interpreted the data analysis and manuscript writing. GW contributed to the conception and conducted the work, drafted the data analysis and reviewed it critically. All the authors approved the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. JPdO, JBdM, JEK, GW accept full responsibility for the finished work and/or the conduct of the study, had access to the data, and controlled the decision to publish. JPdO is the guarantor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer-reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.