A Rare Case of a Molar Pregnancy Coexisting with a Live Foetus in a Patient with Prior Exposure to M-2 Tone in First Trimester in Eastern Uganda: A Case Report

Abstract

Introduction

Although gestational trophoblastic diseases (GTD) is common, its coexistence with a viable twin pregnancy is a rare phenomenon. The occurrence of such a pregnancy, with reports of prior exposure to M2-tone in early pregnancy, has not been documented before. To the best of our knowledge, this is the first of such a case in Uganda.

Case

A 30 years old, black African Ugandan, gravida 3para 1+1 at 19⁺⁴ weeks of amenorrhoea (WOA) presented at Mbale RegionalReferral Hospital (MRRH) in September 2024. She had had a viable term vaginal delivery 5 years ago, that was followed by secondary infertility, for which, no treatment was sought. She subsequently had two natural conceptions. The second pregnancy was lost at 3 months of amenorrhoea following a spontaneous abortion. During the current pregnancy, she was put on M-2 tone (Ayurveda tablets) for 2 months and oral progesterone 10 mg daily till 12 weeks of amenorrhoea. During her fourth antenatal care (ANC) contact, it was noticed that she had gained excessive weight for the WOA. Further assessment revealed exaggerated symphysio-fundal height (SFH). The obstetric scan requested for showed features of viable foetus coexisting with a molar pregnancy. Three prior ultrasound scans had apparently reported a normal pregnancy. Serum beta human chorionic gonadotrophin hormone was very high for WOA. During the pregnancy and peripartum period, she developed obstetric complications but delivered a viable foetus, with a placenta that showed clinical evidence of molar pregnancy. Follow up has revealed resolution of symptoms and no gestational trophoblastic neoplasia (GTN) sequelae.

Conclusion

Molar twin pregnancy with a viable foetus is associated with various maternal and perinatal adverse outcomes and presents management challenges. Whether early pregnancy exposure to M2-tone is a risk factor cannot be elucidated. Close antenatal and postnatal surveillance should be instituted to rule out GTN sequelae.

Introduction

Gestational trophoblastic diseases (GTD) refers to a constellation characterized by abnormal proliferation of the trophoblastic tissue and range from benign to none-metastatic malignant and metastatic malignant lesions. The benign lesions include hydatidiform moles (HM); which include complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM); while the malignant ones, also called gestational trophoblastic neoplasia (GTN) include non-metastatic invasive mole (chorioadenoma destruens), non-metastatic and metastatic malignant choriocarcinoma, and metastatic malignant placental site trophoblastic tumours and Epithelioid trophoblastic tumours.^1–3 The World Health Organization (WHO) 5^th Edition (2021) has been expanded to include mixed trophoblastic tumour which is characterized by an admixture of two or all three of the histological subtypes of the malignancy.²

The incidence of molar pregnancies (MP) varies across regions. The incidence ranges between 0.2 and 9.9 per 1000 pregnancies,^4–6 1 in every 200–400 pregnancies in Brazil,⁷ higher in Asian countries^8,9 up to as high as 28 per 1000 pregnancies in Pakistan.¹⁰ Generally, high-income countries (HICs) report MP ratios from 66 to 121 cases per 100 000 pregnancies, whereas low and middle income countries (LMICs) report ratios from 23 to 1299 cases per 100 000 pregnancies.¹¹

Twin pregnancies as a category of high‑risk pregnancies due to high incidences of adverse outcomes such as intertwin weight discordance, twin-twin transfusion syndrome (TTTS), twin-anaemia-polycythemia-sequence (TAPS) and selective foetal growth retardation (sFGR) is a common phenomenon in obstetrics practice¹² and account for 2–4% of all deliveries.^12–14 However there is a dearth of literature regarding the co-existence of a molar pregnancy with a viable co-twin. That said, three types of molar pregnancies with coexisting normal live foetus are recognized.^15–17

Furthermore, the association of this phenomenon of molar pregnancy with viable co-twin foetus in a gravid with prior exposure to M2-tone is not established. M2-tone, an herbal medicine, has established its estrogenic effect in female infertility. It is largely grounded on Ayurveda, the ancient Indian medical science that identified four requisites for normal healthy pregnancy. These four requisites are – the season (normal ovarian steroid‑dependent status), the good quality viable seeds (healthy male and female gametes), the fertile soil (healthy and conducive endometrial structure) and the water (normal endometrial vasculature). The poor quality of any of these four essentials is believed to lead to infertility.¹⁸ Studies done by Mojisola et al, in Nigeria,¹⁹ and Malhotra N et al revealed that Syrup M2-tone improves endometrial morphology and increases pregnancy rates.¹⁸ There is no association that has been reported between M-2 tone exposure and molar pregnancy.

We present a case of a molar pregnancy coexisting with a normal viable foetus that we managed at Mbale Regional Referral Hospital (MRRH) in eastern Uganda. To the best of our knowledge, this is the first case of the kind reported in Uganda.

Case

We present a 30 year old, Ugandan black African female who presented to the Gynaecologic oncology clinic at Mbale Regional Referral Hospital (MRRH) on 09^th September 2024, as a Gravida 3Para1+1, with last normal menstrual date (LNMP) of 25^th/April/2024, expected date of delivery (EDD) was 02^nd February 2025 and was therefore 19⁺⁴ weeks of amennorhoea.

She had a term spontaneous vaginal delivery about 5 years ago following an uneventful pregnancy. The resultant female is reportedly well and at school. She suffered secondary infertility that she did not seek treatment for. However, she conceived spontaneously in October 2023 but suffered a spontaneous abortion at about 3 months of amenorrhoea. She reports that abortion was completed medically. She later spontaneously conceived in April and was subsequently put on M2-tone tablets (these are herbal Ayurveda tablets for women’s health) for 2 months and on oral progesterone 10 mg daily till about 12 weeks of amenorrhoea.

Significantly in regard to this pregnancy, she had nausea and could spit a lot during the first trimester. It resolved without seeking medication. She booked for antenatal care (ANC) at about 4 weeks of amenorrhoea and was started on folic acid. She was found seronegative for human immune virus (HIV), Hepatitis B and Syphilis. She reports quickening at about 4 months of amenorrhoea. At about 10⁺⁴ WOA (8^th July 2024) she had a febrile illness and was diagnosed with malaria by blood smear microscopy and treated with intravenous artesunate for 7 days. Fundal height was not palpable at this stage and had normal blood pressure (BP) of 122/78mmHg. She had mild spontaneous spotting at about 13WOA that resolved following bed rest.

4 weeks later at the time of the third ANC contact, her BP was 120/87 mmHg but significantly had a Symphysio-fundal height (SFH) of 22/40 with a weight of 92 kilograms. 31 days later when she went for the fourth ANC contact, SFH was 26/40 with a body weight of 94 kg. She had had three ultrasound scans on 21^st June, 16^th July and 4^th September that indicated she had a single intrauterine live foetus with adequate amniotic fluid with no anomalies noted.

Furthermore, she reported that 1 month prior to coming to our unit, the nausea and excessive spitting had reappeared and had been worried by the excessively “big stomach” at such an early gestation.

She reported to be the 9^th child with 3 male and 5 female siblings. None has ever had a complication during pregnancy. She reported that one female sibling had primary infertility. She denied smoking tobacco but occasionally takes alcohol.

She is a lady who had generally been well with no known chronic illnesses and not on any chronic medication. She was known to be allergic to Sulphonamides. She had never had a history of any surgeries or a blood transfusion.

On examination, she had good performance status of 1, afebrile, no jaundice, no dehydration and had oedema grade II but no facial puffiness.

Breasts and thyroid exam were normal.

Blood pressure=125/71 mmHg.

Par Abdomen (P/A): The abdomen was grossly distended in comparison to the weeks of amenorrhoea and anterior abdominal wall oedema was noted. SFH=30 cm. Foetal parts were difficult to palpate (Figure 1).

Figure 1.

Abdomen with a smiling umbilicus, anterior abdominal wall oedema and SFH=30 cm (9 cm higher than the WOA).

Vaginal exam (V/E) was deferred.

Diagnosis: G3P1+1 at 21 WOA with hydatidiform mole with coexisting live foetus (HMCLF)

Work up 9^th Sep 2024 Obstetric ultrasound scan: single live intrauterine foetus with foetal biometry of biparietal diameter (BPD) of 45.2 mm, head circumference (HC)=168 mm, abdominal circumference (AC)=146 mm, Femur length=31.6 mm and with a gestational age =19 weeks 5 days and about 316 grams. Also noted was adequate liquor volume of 13.1 cm amniotic fluid index, fundoposterior non low lying placenta, with bilateral ovarian enlargement with the right measuring 5.6 cm and the left measuring 7.7 cm. Significantly, a large intrauterine heterogeneous mass was seen in the posterior portion with a snow storm appearance and measuring 16.7×8.6 cm.

A repeat obstetric ultrasound scan on 19/September/2024 revealed a single viable intrauterine foetus with normal structures at 20 weeks and 2 days gestation with foetal heart rate of 146 beats per minute (bpm) with posterior placenta but not low lying. Note was made of smooth walled highly echogenic, spongy mass with multiple cystic areas attached to the anterior uterine wall measuring 180x98 mm. A septum was noted separating the mass from the foetus.

Urinalysis was normal with no proteins or red blood cells in urine.

Serum beta human chorionic gonadotrophin (beta hCG) = greater 15000 mIU/L (Efforts to get values of an adequate titer failed)

On 10^th October 2024 (at 24 weeks of amenorrhoea), we reviewed her again. She reported feeling fairly well, she had not had any vomiting or bleeding, and there were no symptoms of heat intolerance.

On examination, her performance status was 2, pedal oedema grade II, no jaundice and no pallor of mucous membranes.

Blood pressure=138/85 mmHg with pulse =83 bpm.

P/A: SFH=32/40 with difficulty to palpate foetal parts and hear the foetal sounds.

A decision was made to start her on tablets labetalol 100 mg once a day for 3 weeks.

Work up

Repeat beta hCG measurements on 10^th October were 617,046.1 miu/mL (0–5)

Interventions: We had a family conference in our Gynaecologic oncology clinic. The patient expressed strong fertility desire and that she had only one child at 30 years of age and suffered secondary infertility and an abortion thereafter. We agreed with the family to continue with the pregnancy and a close watch and act, where required in case of the profound complications which had been explained to the family.

Further work up

21^st October 2024

Beta hCG=546,844 Miu/mL (down from 627,946.1; eleven days ago)

Thyroid function tests:

Thyroid stimulating hormone (TSH) =4.51uIU/mL (0.35–4.94)

Free Tri-iodothyronine (T3) =4.9 pmol/L (2.6–5.7)

Free thyroxine (T4) =10.4 pmol/L (9–19)

Alpha foetal protein (AFP) = 300 ng/mL

Shielded chest x-ray: Mild cardiomegaly with costophrenic to cardiac ratio of 17.2 cm/8.4 cm=2.04

On 29^th October 2024: She was at 26⁺⁶

She was more oedematous than before at grade III with a blood pressure of 145/85mmHg

P/A: SFH=34 cm

We put her on Tablets Labetalol 100 mg twice a day and Tabs Nifedipine 20 mg twice a day. She failed to access labetalol after one week of treatment and was switched to methyldopa 500 mg 8 hrly.

Repeat liver and renal function tests were normal.

She was given intravenous 4 g of 20% magnesium sulphate as loading dose for neuroprotection.

She received intramuscular injection of dexamethasone 6 mg twice a day for two days.

She stayed away, and we could communicate with her on phone.

We asked her almost every week, whether she had had a bleed, how blood pressures were, any blurred vision and or headache, and whether she could feel foetal kicks and the colour of urine.

During our phone conversation, we asked her to do an obstetrics ultrasound scan and return for review on 5^th November 2024. She was not able to return but did a scan, and the findings are reported in Figure 2.

Figure 2.

(A–C): Obstetric ultrasound scan done on 5th November 2024 showing single intrauterine foetus at 27⁺⁶ with estimated foetal weight (BPD, AC, HC and FL) of 1189 grams. Placenta was posterior and not low lying with amniotic fluid index of 19.53 cm. Biophysical profile=10/10. A dense echogenic mass with multiple cystic areas attached to the anterior abdominal wall and a septum separating form the foetus is noted on the right.

On 26^th November, she called in the afternoon reporting about drainage of liquor that had started during the previous night but was not associated with any show or urge to push. She reported no fever and noted that she had experienced over 12 foetal kicks since last night and that she could still experience them. We asked her to get a means and move to hospital.

On arrival, she was calm, with no neurological complications, her BP=126/80 mmHg with a pulse of 97 bpm.

P/A: SFH=38 cm, no palpable contractions. It was difficult to palpate the foetus.

V/E: Speculum exam revealed no active drainage of liquor, and there was no pool in the posterior fornix even on the cough reflex.

Diagnosis: G3P1=1 at 30+4 with Hydatidiform mole coexisting with coexisting live foetus (HMCLF), preeclampsia with no features of severity and preterm premature rupture of membranes (PPROM).

Differentials: placental mesenchymal dysplasia or a large placental chorioangioma

Management

1. Obstetric ultrasound scan with Biophysical profile (BPP) was requested. It revealed estimated foetal weight (EFW)=1760 gm, amniotic fluid index (AFI)=8.7 cm, BPP=10/10. An increase in size of the dense echogenic mass with multiple cystic areas with vesicles attached to the anterior uterine wall and occupying the maternal right was noted with a septum separating it from the foetus (Figure 3).

Figure 3.

(A–D) Obstetric ultrasound scan done on the day she had leakage of liquor on 26th Nov 2024. Compared to the obstetrics scan done on 5^th November (A–D) 2024: EFW=1760 gm, AFI=8.7 cm, BPP=10/10. An increase in size of the dense echogenic mass with multiple cystic areas with vesicles attached to the anterior uterine wall and occupying the maternal right was noted with a septum separating it from the foetus (B).

2. Blood was taken off for serum beta HCG, full haemogram, and renal and liver function tests. The CBC, LFT and RFTs were all normal. Serum beta hCG=3,986,766.1 mIU/mL.

3. Bed rest.

4. Tablets azithromycin 2 g start.

5. Tablets Drotaverine 80 mg 8 hrly for 5 days.

6. Repeat dose of intramuscular dexamethasone 6 mg 12 hrly for 48 hours.

At 01:20 hrs on 27^th November 2024, she went into established labour and delivered a female baby with birth weight=1.5 kg, Apgar score of 9¹–10⁵. Baby was given 0.5 mg of intramuscular vitamin K and tetracycline eye ointment. Child was admitted in neonatal intensive care unit (NICU) and discharged 96 hours after admission.

Mother suffered primary postpartum haemorrhage (PPH) and was taken to theatre for suction evacuation and gentle sharp curettage, the contents of which are shown in Figure 4.

Figure 4.

Uterine contents evacuated after the patient suffered primary PPH. Note the grape like contents. Follow up beta Hcgs pre and post delivery.

Unfortunately, during the emergency management, one of our support staff disposed the contents, and we did not do histology. We transfused her with two units of whole blood.

Post Transfusion Full Haemogram

Haemoglobin concentration: 8.2 g/dl with low mean cell haemoglobin concentration, low mean cell haemoglobin and low mean cell volume.

Platelets =151x10³/uL (150–450). Renal function tests were normal.

Liver function tests were deranged as follows

Total protein=52.89 g/l (60–85) with albumin=28.46 g/l(30–55)

Alkaline phosphatases=180 U/L (0–170) and Gamma Glutamyl Transferase (GGT) =68.2 U/L (10–55)

Beta HCG 12 hours after delivery=348606 mIU/mL (0–5); a drop from 3,986,766.1 mIU/mL pre-delivery (91% drop).

Blood pressure 133/89 mmHg (she was still maintained on tablets of methyldopa 250 mg once a day and nifedipine 20 mg once a day)

She reported intermittent PV bleeding that began on 23^rd Dec 2024 with two episodes of clots on 23^rd Dec 2024 and 04 January 2025

Follow up of the Baby

27^th Nov 2024-Birth weight =1.5 kg. Child was admitted in the neonatal intensive care unit (NICU) and the care of the Paediatrics and child health specialists. Baby was discharged from the NICU. Child was discharged from NICU on 1^st December 2024. Mother was put on contraception.

6^th Dec 2024-weight of baby =1.255 kg

23^rd Dec/2024-weight of the baby=1.535 kg with occipital frontal circumference (OFC) =30.2 cm.

As per July 2025, baby and mother are all doing well. Mother is off antihypertensive therapy.

11^th October 2025: No complications. Both mother and baby are doing well.

We followed up this mother, and Table 1 and Table 2 show the Serum beta human chorionic gonadotrophin (beta hCG) levels pre-delivery and the postpartum trends (Table 1 and Table 2). Levels normalized after 5 months (Table 2) and Figure 5 summarizes the percentage drops with time.

Table 1.

Serum Beta Human Chorionic Gonadotropin Hormone Trends During the Antenatal Period

Date Taken	Beta HCG mIU/m L(0–5)	Weeks of Amenorrhoea	% Increase in Beta hCG	Blood Pressure Value
19th/09/2024	>15000 (Not able to get absolute value)	21	–	125/71mmHg
10th/10/2024	617,046	24	–	138/85mmHg
21st/10/2024	546,844	25 and 4days	−11.4%	–
29th/10/2024	2.5349138x106	26 and 5 days	78.4%	148/85mmHg
21th/11/2024	3.9867661 x106	30 and 1 day	145.2%	130/76mmH

Table 2.

Serum Beta Human Chorionic Gonadotropin Hormone Trends During the Postpartum Period

Date Taken	Beta HCG mIU/mL (0–5)	Postpartum Period	% Drop in Beta HCG value	Blood Pressure
27th/11/2024	348,606	12 hours	91.3% in 12 hours	133/89mmHg
04/12/2024	6367	7days	98% in 7days	130/84mmHg (on tabs Nidepine 10mg once a day)
11/12/2024	987.3	14days	84.5% in 7days	131/87mmH
23rd/12/2024	179	26days	81.7% in 12 days	121/86mmHg (stopped antihypertensive drugs)
06th/01/2025	75.4	40days	57.8% in 14days	116/80mmHg
20th/Jan/2025	29.4	54days	61% in 14 days	121/74mmH
03/Feb/2025	20.9	68days	28.9% drop in 14 days	116/76mmHg
04/March/2025	4.52	94days	78.4% drop in 29days and normal	118/78mmHg
22.April.2025	< 2	140days	Normal	120/80mmHg
29th.May.2025	0.455	177 days	Normal	117/80mmHg
07th July 2025	Less than 0.2	216 days	Normal	115/78mmHg
11th Oct.2025	0.1	312days	Normal	120/76mmHg

Figure 5.

Graph showing trends of human Chorionic gonadotropin hormone levels (mIU/mL) during the postpartum period.

Discussion

Gestational trophoblastic diseases (GTD) refers to a constellation characterized by abnormal proliferation of the trophoblastic tissue and range from benign to none-metastatic malignant and metastatic malignant lesions. The incidence of hydatidiform mole (HM) varies across regions. The incidence ranges between 0.2 and 9.9 per 1000 pregnancies,^4–6 1 in every 200–400 pregnancies in Brazil,⁷ higher in Asian countries,^8,9 up to as high as 28 per 1000 pregnancies in Pakistan.¹⁰ Generally high-income countries (HICs) report HM ratios from 66 to 121 cases per 100 000 pregnancies, whereas low and middle income countries (LMICs) report ratios from 23 to 1299 cases per 100 000 pregnancies.¹¹ The consistent risk factors for GTD are extremes of ages (younger than 20 and above 40 yrs)^20,21 and history of a molar pregnancy.²⁰ This association, although applicable for both complete and partial moles, is much greater for CHM at all maternal ages, and the degree of risk is much greater with older (≥45 years) rather than younger (≤15 years) maternal age.²¹

Furthermore, although twin pregnancies present in 2–4% of deliveries and are much more common in Africa and Asia,^12–14 those in whom a molar pregnancy coexists with a viable pregnancy is a rare phenomenon in Obstetrics and Gynaecologic oncology practice. To the best of our knowledge, this may be the first documented case in Uganda.

Hydatidiform moles (HM) typically result from intrinsically abnormal conceptions characterized by excessive proliferation of trophoblast and by relative placental over-expression of paternally derived genes. However, there seems to be an increase in prevalence of this condition with the advent of assisted reproductive therapy (ART). In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) increase the frequency of molar pregnancy to 2 per 10,000 pregnancies.^22–24

From aetiopathogenic, clinical, and prognostic perspectives, HM manifests as either complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM). CHM results from the fertilization of an enucleate oocyte by a haploid sperm that subsequently duplicates its DNA (endoduplication) or, less commonly, by two haploid sperms. In both cases, the resulting conception is a diandric diploid of parthenogenetic origin, either 46 XX or 46 XY, leading to diffuse trophoblastic proliferation, marked hydropic oedema of the chorionic villi, absence of scalloping of villi, and absence of an embryo/fetus or its appendages. In contrast, PHM typically arises from the fertilization of a genetically normal oocyte by two haploid sperms, or by a single sperm that undergoes endoduplicates, resulting in a diandric triploid conceptus with both maternal and paternal genetic contributions. This chromosomal composition allows for some embryonic and extraembryonic development. In rare cases where fetal development progresses, it is usually associated with multiple anomalies incompatible with life, and pregnancy rarely extends beyond the second trimester. In such cases, the trophoblastic tissue displays less intense, focal proliferation, with minimally hydropic villi confined to trophoblastic islands.^1,21,25 The risk of progression to GTN is higher with CHM, 15–20%, compared to less than 5% for PHM.^1,25

The World Health Organisation (WHO) reports that 70–80% of the African population relies on traditional and complementary medicines (TCM) to meet their primary health care (PHC) needs.²⁶ There is further evidence of increased utilisation^27,28 and influx of Ayurveda largely driven by strong Indo-African ties and global market interests.²⁹ Although M2-tone, an herbal medicine has been established to have various positive therapeutic effects in reproduction through its estrogenic effect in female infertility,^18,19 its association with molar pregnancy has not been elucidated. Suffice to note is that these trials involved women undergoing assisted reproductive technology (ART) and M2-tone were introduced prior to conception. In our case this drug was introduced during the early first trimester. She was given M2-tone and oral progesterone for two months till 12 weeks of amenorrhoea. Although it is not documented why that was done, and mother did not clearly understand why, we envisage that since the pregnancy followed a pregnancy loss in the first trimester in Jan 2024 and was given alongside oral progesterone, it have been for corpus luteal phase support. We could not come across literature where M2-tone had ever been given for that indication though. The studies we came across indicate use of Ayurveda herbal in patients already afflicted by molar pregnancies,^30,31 though the constituents are different from those of M2-tone.³² Given that this is the first case where M2-tone has been used, we cannot assert that M2-tone is associated with molar pregnancy.

The existence of a molar pregnancy with a viable co-twin is an extremely rare pregnancy event with an estimated incidence of 1/20,000–100,000 pregnancies.³³ To the best of our knowledge, only one case has ever been reported from East Africa (Uganda, Kenya and Tanzania) and that case was from Kenya.³⁴ The patient reported from Kenya had naturally conceived just like in our patient. Both cases had never suffered a molar pregnancy before.

There are three types of molar pregnancies with coexisting normal live foetus: the most frequent case is a twin pregnancy with one normal fetus having a normal placenta and another complete mole;^15–17 the second type is a twin pregnancy with regular foetus and placenta and another partial mole³⁵ and the third, and most rare one, is a singleton normal foetus with partial molar placenta.³⁶ The latter type was reported to occur in 0.005 to 0.01% of all pregnancies.³⁷ We were not completely able to discern with certainty the type in our case, but clinical and radiological features point to the first type in this case.

Molar pregnancy coexisting with a normal foetus is referred to as a sad foetus syndrome (SFS).³⁸ Molar pregnancy coexisting with a living foetus represents a diagnostic and management challenge particularly in low income settings like Uganda with limited diagnostic capabilities in maternal foetal medicine to aid prenatal diagnosis by chorionic villus sampling (CVS) or amniotic fluid test (AFT) is the most effective method for determining foetal karyotypes to exclude foetal triploidy. DNA polymorphism analysis should be requested for the diagnosis of hydatidiform mole, especially in cases where it is difficult to discriminate between PHM mole and HMCF.³⁹ The diagnostic challenge of a case of molar pregnancy with a coexisting living foetus is to differentiate two different conditions; singleton conception with a partial mole and dizygotic twins consisting of normal fetus with a complete mole. If the ultrasound picture of a normal fetus of an appropriate size for its gestational age together with an abnormal cystic placenta, a twin pregnancy consisting of a normal fetus and a CHM should be suspected,³⁹ just like in our case.

Ultrasound scan (US) examination is typically a reliable method of diagnosing hydatidiform mole and a co-existing foetus (HMCF). However, HMCF is often missed at early gestational age because abnormal placental echoes are often mistaken as subchorionic haematoma, placental haemangioma, and accidental haemorrhage, which could be differentiated easily using 2D US, associated with Doppler examination and magnetic resonance imaging (MRI). In a study by Liang et al only 47.06% (8/17) of patients had been diagnosed before 12 weeks of gestation.³⁹ In our case, the patient presented in the second trimester at 19⁺⁴weeks of amenorrhoea, and had had 3 prior ultrasound scans that were all normal. HMCF may be mistaken for placental mesenchymal dysplasia (PMD), which is a rare placental vascular anomaly because they have similar US characteristics.³⁹ We did not have MRI in this region or in the country.

The obstetric ultrasound scans that we had at all gestational ages showed a foetus with no anomalies and appropriate for gestation age. Although a twin peak sign, also called lambda sign, and the T-sign, on ultrasound are used to diagnose twin pregnancy, absence does not, with certainty, rule it especially if imaging is done beyond 14 WOG. Although the “twin peak sign” in which chorionic tissues extend into the inter-twin membrane, forming a triangular echogenic structure that intervenes the normal twin sac and the molar pregnancy, confirm the presence of a dichorionic twin gestation,³ it was not revealed in this case. It is worth noting that the first ultrasound scan in our patient was done at 19 weeks 5 days of gestation.

Although it is unfortunate we were not able to get hold of the placenta (dumped by the support staff during our resuscitation of the mother), our case by clinical, radiological and biochemical beta hCG results points more to one with normal foetus with a complete mole. She had early onset of preeclampsia without severe symptoms at 26 weeks and 6 days of amenorrhoea with sympsio-fundal height at 34 cm (discrepancy of 7 cm) with several obstetric ultrasound scans showing a dense echogenic mass with multiple cystic areas with vesicles attached to the anterior uterine wall and occupying the maternal right with a septum separating it from the foetus (Figures 2 and 3). The ultrasound scan done at 21 WOA indicated theca lutein cysts with the right and the left measuring 5.6 cm and 7.7 cm, respectively. Other diagnoses such as placental mesenchymal dysplasia (PMD) and Chorangioma could not be ruled out. Histopathology could have helped resolve it but serum beta hCG point much more towards hydatidiform mole.

In a literature review published by Kawasaki et al,⁸ eighteen cases of molar pregnancies and coexisting living foetus were reported. The mean gestational age at delivery was 24.5 weeks, and only four foetuses (22.2%) survived extrauterine. On karyotyping, placenta was diploid in ten cases, indicating that they may be a CHM in a twin pregnancy or associated placental mesenchymal dysplasia that was also reported by Hojberg et al,⁴⁰

Furthermore, retrospective case series of 13 patients with complete hydatidiform mole and coexistent normal fetus (CHMCF) by Giorgione et al in which the study aimed to describe prenatal diagnosis and the outcome, 6/13 (46%) had subchorionic haematoma on first trimester ultrasonography (US) and anomalies, two women decided to terminate their pregnancies; 4 ended in late miscarriages (36%, 4 of 11) between 13 and 21 weeks, and early neonatal death occurred in 1 case (9%, 1 of 11); 5 women delivered a live baby with a mean gestational age of 31 weeks (range 26–37 weeks) with an overall neonatal survival of 45% (5 of 11). Significantly, GTN occurred in 31% of cases (4 of 13).⁴¹

Notwithstanding, a case series reported from Mansoura University, Egypt from September 2015 to August 2020, 12 cases were reported. Twelve pregnancies were analyzed with a mean maternal age of 26.0 years and the median parity of 1.0 (range 0–3). Additionally, the duration of the pregnancies ranged from 14 to 36 weeks with median serum hCG was 165,210.0 U/L (range 7662–1,200,000). Of the twelve foetuses, three foetuses (25%) survived with one dying at 5 months of age due to congenital malformations such as hydrocephalus. Furthermore, 10 of the 12 patients had histologic diagnosis. Of the 10, 60% (6/10) revealed complete mole associated with a normal placenta and partial mole in 4 cases (40%). Maternal complications occurred in 6 (50%) cases with the most common being severe vaginal bleeding in 4 (33.3%) cases. Serum beta-hCG levels were not significantly associated with maternal complications. Of the seven pregnancies that were carried beyond 20 weeks, five ended in premature deliveries (71.4%).⁴²

From the above literature review by Kawasaki,³⁶ case series by Giorgione et al,⁴¹ and Hemida et al,⁴² the diagnosis of this condition remains a dilemma and is associated with poor maternal and neonatal outcomes. The incidences of obstetric and neonatal complications are beyond the baseline population levels.⁴³

Obstetric complications such as hypertensive disorders of pregnancy (HDP) with or without severe features, hyperemesis gravidarum, and hyperthyroidism are known to set in earlier in gestation compared to other pregnancies.^16,33,39,44 Other complications reported include intrauterine growth restriction,^45–47 oilgohydramnios, and foetal hepatic cyst,⁴⁵ pregnancy associated bleeding par vaginum,^{24,34,45,47,48} intrauterine infection with group B streptococcus,³⁴ preterm birth and high rates of admission to neonatal intensive care unit, and spontaneous abortion.³³ Santos et al reported second trimester onset of hyperemesis gravidarum and hyperthyroidism with serum beta hCG of 1.891264x10⁶ mIU/mL that led them to termination of pregnancy.⁴⁴ Relatedly, in our case there was no hyperemesis gravidarum and no clinical and biochemical demonstration of hyperthyroidism despite serum beta hCG levels reaching as high as 3,986,766.1mIU/mL (Table 1 above). Furthermore, in this case preeclampsia without severe features set in at 26⁺⁶ WOA. Cases of HDP have been reported in other cases.^16,42,44,49 A case series in Egypt reported no positive correlation between serum beta HCG levels and manifestation of maternal complications.⁴²

Additional complication noted in our case is preterm premature rupture of membranes (PPROM) at 30⁺⁵ WOA. PPROM in a partial molar pregnancy coexisting with a normal diploid female foetus at 32 weeks of gestation (WOG) has been reported before by Hsieh et al.³⁵ Just like in our case, the birth weight was 1.5 kilograms and therefore had intrauterine growth restriction.⁵⁰ A case of a diploid female coexisting with a partial mole and placentomegally in a 25 year old mother has been reported.³⁶ Cases of normal male babies have also been delivered as reported by Pasquale et al,⁴⁶ Changchien et al,¹⁶ and Khanom et al.⁴⁹ Currently, there seems to be no predilection of hydatidiform mole coexisting with a live foetus (HMCLF) to a particular foetal sex.

There seems to be no consensus on management of HMCLF with much of what we know and practice largely drawn from case series and case reports. However, what is clear from the case series and reports is that it is associated with worse perinatal and maternal outcomes compared to the other pregnancies. The decision to continue with the pregnancy or induce abortion is largely dependent on a shared respectable decision‑making process but is largely influenced by the presence or absence of life‑threatening complications such as massive haemorrhage, HDP with severe features (and its control), viability and status of the foetus and the biophysical profile and the institutional factors to manage this complex case.

Our mother was a 30 yr old G3P1+1, with a 5 years old daughter, had had an abortion and been diagnosed with secondary infertility though no interventions had been taken in that regard. She had had spotting at about 13 WOA that resolved following bed rest. We had a family conference with the partner and sister when she was 24 WOA and explained to them the diagnosis and possible outcomes, and the decision to continue with the pregnancy and close surveillance, was made. This approach has been reported to work and yield positive results.⁴⁷ Although this complex condition is hard to manage, the involvement of the family is key. Cases of respectable disagreement between Obstetrician and the pregnant woman in which the former suggests abortion while the latter insists on carrying on with the pregnancy have been reported.³⁴ In whichever case, the patient’s wishes ought to be respected and supported throughout the professional engagement.

In cases where the pregnancy is continued, the likelihood of a live birth ranges from 37%⁵¹ to 60%.⁵² The mode of delivery of HMCLF is not definite but team decision-making is desirable supported by maternal and foetal condition. Hsieh et al,³⁵ Pasquale et al,⁴⁶ and Kawasaki et al³⁶ have all reported cases of partial mole with coexisting normal baby delivered by emergency caesarean section (EmCS) at 31, 32 and 25 WOG in parturients aged 30 years, 37 years and 25 yrs, respectively. The decision to do emergency caesarean section was informed by maternal and or foetal compromise. Furthermore, Changchien et al reported a case of complete mole with coexisting live male baby that was delivered at 23 WOG by EmCS due to chorioamnitis.¹⁶ Chen et al also reported a term baby boy who was delivered at 38 WOG and weighing 3380 g by EmCS due to cephalopelvic disproportion. Significantly, this case went to term because the woman had no complications.¹⁵

In our case, the maternal and foetal assessments were not worrying and complications had been managed despite the ever increasing serum beta hCG. We had hoped to push the pregnancy to term or near term as much as possible. We did a shielded chest x-ray that showed no evidence of cannon balls at 27 WOG. Given that we do not have invasive prenatal diagnostic capabilities and the patient could not outsource them, continued monitoring with history taking (both physical and phone conversations), physical exam, biochemical tests to ascertain the major organ functionality and beta serum hCG levels, coupled with diagnostic radiological investigations, were instituted. Our mother gave birth to a preterm vaginally and suffered primary postpartum haemorrhage (PPH) that warranted activation of the PPH bundle⁵³ and subsequent suction evacuation and sharp gentle curettage in theatre under anaesthesia. She was transfused with two units of blood post evacuation. Baby was admitted to the NICU and managed by the Paediatrics and child health team and successfully discharged after 96 hours. Child growth and developmental milestones assessment do not reveal any negative outcomes such as cerebral palsy (CP). With regard to management, we highly anticipated preterm delivery with antecedent complications such as neurological deficit and respiratory distress syndrome (RDS). Antenatal corticosteroids (ACS) are reported to accelerate type 1 and type 2 pneumocyte development, leading to structural and biochemical changes that improve both lung mechanics and gas exchange, and should preferably be given within 1–7 days of planned delivery to achieve maximum efficacy and at least 23 WOG.⁵⁴

Prematurity is a recognized major risk factor for respiratory distress syndrome (RDS) and cerebral palsy. Remedies such antenatal steroid and magnesium sulphate administration have been reported to be of therapeutic benefit. While magnesium sulphate reduces relative risk (RR) for CP, steroids reduce the RR for both RDS and CP.⁵⁵ Our mother had received 6 mg of intramuscular dexamethasone twice a day for two days and 4 g of 20% intravenous magnesium sulphate at 26⁺⁶ WOA and received a another short of intramuscular dexamethasone 6 mg at 30+⁶ WOA on the day of delivery.

Cases of HMCLF that went on to have vagina delivery with the aforementioned complications have been reported in literature. Camacho-Montaño et al reported a case of a 19 yr old prime gravida who delivered by spontaneous vaginal delivery, a live female foetus at 33 WOG with birth weight of 900 g following 6 hrs of labour in Colombia and had PPH. However in contrast to this case in Colombia, our mother did not develop worsening preeclampsia with features of severity that required intensive care unit admission in the immediate postpartum period.⁴⁵ That notwithstanding, cases of spontaneous vaginal delivery of a normal live term baby with no postpartum complications have been reported. Libretti et al reported a 40 yr old Caucasian woman who delivered a term baby with no complications thereafter.⁵⁶ Rathod et al reported 24 yr old G2P1+0 who delivered at 28 WOG preterm male fetus weighing 1.32 kg.³⁸

The clinical and laboratory diagnosis of maternal or neonatal anaemia that is common in these cases is largely due to pregnancy-associated haemorrhage with severe par vagina bleeding.⁴⁸

Aside from the above-mentioned adverse neonatal and maternal events, there is a risk of GTN sequelae. Several studies have reported prevalence rates from case series; Hemida et al from Egypt reported a prevalence rate of 8.5% (1/12) from a series of 12 cases chemotherapy,⁴² Kutuk et al reported 1/7 (14%) prevalence in their case series and was managed by hysterectomy,⁵⁷ Sebire et al reported a rate of 19.4% (15/77),³³ Giorgione et al reported a rate of 31% from a case series of 13 patients.⁴¹ Liang et al have reported 17 cases including 2 cases that had a term deliveries. Although both HMCLF one had preeclampsia and bleeding with hCG of 914,000 mlU/mL, one with hCG of 924,100 mlU/mL remained largely asymptomatic. Of the 17 cases, 6 were partial moles and the highest serum beta hCG was 449,078 mlU/mL. Only one case reached levels of 1,000,000 mlU/mL.³⁹ In this case series, prevalence rate of GTN was 47.06% (8/17), with seven cases managed and cured by one of the single-agent Methotrexate or Dactinomycin protocols, and one treated with multiple-agent chemotherapy due to resistance to single-agent chemotherapy, and subsequently died from the side effects of chemotherapy. The risk of GTN for patients with live birth was 25.0% (1/4). However, the GTN rate of 2 patients who ended their pregnancies with term delivery was not significantly higher compared with the rates for patients who ended their pregnancies with preterm delivery.³⁹ Additionally, Sebire et al study showed that although CHM and healthy co-twin pregnancies have a high risk of GTN from 15%–20% to 27%–46%,^33,58,59 there was no difference in the rates of GTN for those that had termination in the first trimester versus those that carried on with the pregnancy.³³ Our patient is 8 months postpartum and has had resolution of beta hCG and HDP. Therefore, we can confidently conclude that there is no sequelae of GTN.

Previously, it was considered that termination of the pregnancy was the ideal method of management due to the risk of complications associated with this kind of pregnancy. However, with recent advances geared towards better maternal-foetal outcomes, the continuation of the pregnancy with the delivery of a healthy newborn is possible. It has also been postulated that hCG levels up to 400,000 IU/l are considered the best indicators for a better perinatal outcome.^60,61 In our case, the median quantitative beta hCG was 1.54×10⁶ IU/l with the highest being 3.987×10⁶ IU/l on the day of delivery.

From the clinical point of view, this kind of twin pregnancy must be differentiated from placental mesenchymal dysplasia and chorioangioma. The former is a benign vascular condition characterised by the enlargement of the placenta with multiple cysts. Although hCG can be increased in this condition, predominantly alpha-fetoprotein (AFP) is raised. In our case only one AFP test was done and was 300 ng/mL. We did not seek the continued request for this test since it is paid for out of pocket and costs as much as 10 dollars in our setting. The need to differentiate this condition from the former is better perinatal prognosis associated with placental mesenchymal dysplasia. Chorioangioma is usually focal but can vary in size. On ultrasound, they typically appear hypoechoic with cysts taking up the colour at Doppler imaging. AFP can be raised in this condition. It can be associated with congenital anomalies.⁶⁰ As discussed, serum beta hCG as high as millions are rare PMD and chorioangioma.

Conclusion

We present a case of twin pregnancy with live foetus coexisting with a molar pregnancy with prior exposure to M2-tone in early first trimester. Although the mother developed several pregnancy adverse events, it was feasible to manage such a high‑risk pregnancy with positive maternal and perinatal outcomes. The association of M2-tone with molar pregnancy needs further surveillance. Multidisciplinary approach is key in such a case. Although here is no clear consensus to date regarding the best management approach, continuation of pregnancy may be considered after thorough counseling and shared decision-making. In such cases, we propose close antenatal and postnatal surveillance until at least 6 months post normalization of serum β-hCG levels during which period the patient should be on contraception.

Funding Statement

There was no any funding for work in this case report.

Patient’s Perspective

During the family conference, the patient and her family appreciated the efforts of the team to her during this rare kind of pregnancy and promised to comply with the recommendations of the medical team. She informed us, all along we had been dealing with one of our professional colleague. “In fact I am a midwife”, she said.

She was very grateful to the team at MRRH.

“I am really grateful for standing with me and enabling me have a normal daughter”. For this I will forever be grateful, she said.

Abbreviations

ACS, Antenatal corticosteroids; ART, assisted reproductive therapy; CHM, Complete Hydatidiform mole; HM, hydatidiform mole; HMCF, Hydatidiform mole with coexisting foetus; GTD, Gestational trophoblastic disease; GTN, Gestational trophoblastic disease; HDP, Hypertensive disorders of pregnancy; ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilization; MRRH, Mbale Regional Referral Hospital; HMPCLF, molar pregnancy coexisting with a live foetus; NICU, neonatal intensive care unit; PPROM, Preterm premature rupture of membranes; PPH, postpartum haemorrhage; RDS, respiratory distress syndrome; WOA-Weeks of amenorrhoea; WOG, Weeks of gestation.

Data Sharing Statement

There is no data base generated for this case report.

Ethics Approval

There was no need for institutional ethical approval from Mbale Regional Referral Hospital ethics committee (Mbale REC) to publish the case.

Consent to Publish

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.