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CASE REPORT
Ahead of print publication  

Molar pregnancy with a coexistent fetus following assisted reproductive techniques: Two case reports


1 Department of Obstetrics and Gynaecology, AFMS, New Delhi, India
2 Department of Medical Informatics, AFMS, New Delhi, India
3 Department of Community Medicine, AFMS, New Delhi, India
4 Department of Anaesthesia, Rainbow Children's Hospital, Bangalore, India

Date of Submission28-May-2022
Date of Decision05-Aug-2022
Date of Acceptance10-Oct-2022
Date of Web Publication13-Jan-2023

Correspondence Address:
Seema Rai,
Department of Obstetrics and Gynaecology, AFMS, New Delhi
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmms.jmms_90_22

  Abstract 


Hydatidiform mole with the coexisting live fetus is a rare entity occurring in 0.005%–0.01% of all pregnancies. With the introduction of assisted reproductive techniques (ARTs), a significant rise in the incidence of multiple pregnancies has been reported. Here, we report two cases of molar pregnancies with a coexisting live fetus conceived following assisted conception. In our first case, pregnancy was continued and delivered a term live infant. The second case was aborted at 16 weeks' gestation due to maternal complications. These two patients needed chemotherapy due to persistent gestational trophoblastic disease. The rarity of this condition poses several diagnostic and management challenges, especially conceiving after ART the decision of termination for such couples.

Keywords: Coexistent fetus, hydatidiform mole, persistent gestational trophoblastic disease



How to cite this URL:
Rai S, Yasaswi K, Raj R, Hiremath RN, Ghodke S. Molar pregnancy with a coexistent fetus following assisted reproductive techniques: Two case reports. J Mar Med Soc [Epub ahead of print] [cited 2023 Feb 1]. Available from: https://www.marinemedicalsociety.in/preprintarticle.asp?id=367697




  Introduction Top


Gestational trophoblastic disease (GTD) consists of a wide spectrum of conditions ranging from premalignant forms called molar pregnancies which consist of complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) and comprise over 90% of GTD,[1] and malignant forms called gestational trophoblastic neoplasia (GTN) which consist of invasive mole, choriocarcinoma, and placental site trophoblastic tumor. Hippocrates himself described GTD as "dropsy" of the uterus around 400 B.C.[2] The incidence of molar pregnancy in Asia is 1–2/1000 pregnancies. The incidence of hydatidiform mole with a coexistent normal fetus is 1 in 20,000–1 in 100,000 pregnancies in the past but is showing an upward trend with the introduction of assisted reproductive techniques (ARTs).[3],[4] PHM or twin pregnancy with CHM coexisting with a normal fetus (CHMCF) falls into this category.

In this report, we present two such cases; our first case pregnancy was continued and delivered a term live infant. The second case was aborted at 16 weeks' gestation due to maternal complications. These two patients needed chemotherapy due to the development of persistent gestational trophoblastic disease (PGTD).


  Case Reports Top


Case 1

A 25-year-old female with gravida 2, para 1 was treated as a case of secondary infertility and conceived after intrauterine insemination, ovulation induction with letrozole, and human menopausal gonadotropin (HMG). Later on, the patient was lost for follow-up (the patient sought routine antenatal care in a local nearby hospital due to domestic issues) after she conceived and came for a routine antenatal visit at around 23 weeks of gestation. Her first trimester was uneventful and did not have any history of bleeding per vaginum. Her general and systemic examinations were unremarkable; the uterus was found at approximately 24 weeks of gestation. Ultrasound examination at 23 weeks of gestation showed a 102 mm × 78 mm × 88 mm size honeycombed appearance mass secondary to multiple small vesicles toward the right side adjacent to the posterior placenta and a normal developing live fetus at 24 weeks 3 days' gestation [Figure 1]. Her basic antenatal tests and anomaly scan were normal. The couple was counseled about the complications of molar pregnancy to the mother and fetus. The decision was taken to continue the pregnancy. Close monitoring of the patient with human chorionic gonadotropin (HCG), thyroid-stimulating hormone, complete blood count, blood pressure (BP), and frequent scans were done. She was given steroids at around 28 weeks of gestation. At 37 weeks 1 day gestation, the patient was admitted with labor pain and vaginally delivered an alive female baby with an Apgar score of 9/10 and a weight of 2.9 kg, and there was no postpartum hemorrhage. The placenta weighed approximately 500 g and measured 14 cm × 12 cm × 3.5 cm, and the molar tissue was distinct, adjacent to the normal placenta with numerous hydropic translucent vesicles [Figure 2]. The histopathology of the placenta was reported as normal placenta, and molar tissue showed features suggestive of PHM. Karyotyping of the mole and the fetus could not be done. Serum HCG sent 48 h after delivery was 3785.4 mIU/ml. During her weekly follow-up, serum HCG levels began to rise more than 10% of three values over 2 weeks. USG pelvis reveals a 17 mm × 16 mm × 13 mm size ill-defined complex echoic intramural lesion with high vascularity in the uterine body and a 24 mm × 22 mm × 20 mm size cyst in the left ovary [Figure 3]. Chest X-ray was normal. The patient was diagnosed as low-risk GTN (risk assessment score was 2) and started on an 8-day multidose methotrexate protocol with intervening folinic acid. HCG levels fell steadily and returned to normal after 7 months of chemotherapy; USG pelvis showed a complete remission. One year after the completion of treatment, there is no evidence of disease recurrence.
Figure 1: (a) Ultrasound image showing placenta with multiple cystic spaces, (b) Ultrasound image of the patient at gestational age of 23 weeks, showing fetal head next to molar tissue, (c) Ultrasound image showing fetus with normal placenta

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Figure 2: Molar tissue and normal placenta after delivery at 37 weeks

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Figure 3: (a) Ultrasound image of an ill-defined vascular region intramurally, (b) Ultrasound image of the left ovarian cyst

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Case 2

A 27 year old primigravida, with 8 years of primary infertility got conceived through in vitro fertilization (IVF) embryo transfer (ET). Following ovarian suppression with leuprolide (gonadotropin-releasing hormone) analog, follicular growth was stimulated using Gonal (recombinant FSH). Moreover, two 6–8-cell embryos (grade 1) were transferred into the uterus 3 days after oocyte retrieval. The patient was kept on luteal phase support. Serum HCG level was 964 mIU/ml on day 18 following embryo transfer. On day 21, a small intrauterine gestational sac was seen; follow-up ultrasonography after 2 weeks showed a single live intrauterine gestational sac. At 9 weeks of gestation, the patient presented with 2–3 episodes of vaginal bleeding. Ultrasonography showed molar-like changes adjacent to normal-looking fetus at 8 weeks 5 days' gestation in another gestational sac [Figure 4]. The GTD and related risks were explained to the couple. The pregnancy was continued as per her preference, and she was closely monitored in our hospital.
Figure 4: (a) Twin gestation with live fetus at 8 weeks' gestation along with adjacent molar tissue, (b) Ultrasound image of normal-looking placenta and molar tissue at 13 weeks, (c) Ultrasound showing fetus at 13 weeks with normal placenta

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At 12–13 weeks' scan revealed a structurally normal-looking fetus with gestational age of 13 weeks 2 days' with NT of 1.1 mm and nasal bone with multiple tiny cystic spaces, adjacent to normal looking placenta [Figure 4]b and [Figure 4]c. On dual markers test, serum HCG was high for that gestational age (482 ng/ml), and PAPP A at 8.53mIU/ml. For more precise diagnosis, the patient was offered a genetic analysis of amniocentesis, which was accepted by the couple. At 16 weeks of gestation, the patient reported an excessive vaginal bleeding; on arrival, her pulse rate was 112/min, BP was 80/60 mmHg, and pallor was present. The chest was clear, the abdominal finding was 18 weeks' gravid uterus, and the fetal heartbeat was positive. On vaginal examination, there was more than 800 ml of blood loss along with grape-like vesicles, and spontaneous abortion was followed. Her investigations were sent, HB was 6 g/dl, and the rest were within the normal limit.

A female fetus was expelled with no grossly detectable anomalies weighing around 180 g along with a normal-looking placenta weighing approximately 100 g and molar tissue weighing approximately 400 g [Figure 5]. The patient received 3 units of blood transfusion. An ultrasound after abortion confirmed retained products of conception. Suction evacuation was performed under a short general anesthesia. Postprocedural ultrasound confirmed an empty uterine cavity. Chest X-ray was normal. HCG 2 days after termination was 433,511 mIU/ml. The patient was on serial HCG level follow-up; at the 4th week, serum HCG levels began to rise more than 10% of three values over 2 weeks. Her GTN workup was within the normal limits. The patient was classified as low-risk group risk assessment score was 1 and was treated with an 8-day multidose methotrexate protocol intervening with folinic acid. Postchemotherapy, serum HCG concentrations showed a steady fall and reached to the normal value after 5 weeks following chemotherapy, and the patient remains under surveillance. Microscopic examination of the molar tissue showed features suggestive of PHM. The placenta showed no specific pathology. These morphological features allowed the diagnosis of a twin pregnancy consisting a partial mole and normal fetus with placenta [Figure 6].
Figure 5: Fetus and normal placenta with adjacent molar tissue after abortion at 16 weeks

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Figure 6: (a) Section showing hydropic chorionic villi from the molar tissue (×10) view, (b) Section showing irregular-shaped villi (×4) view

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  Discussion Top


Twin pregnancy with hydatidiform mole and coexisting fetus has an estimated incidence between 1 in 10,000 and 1 in 100,000 gestations[3] and may be increased due to the use of ART.[5] Several risk factors associated with molar pregnancy are previous molar pregnancy, advanced maternal age or under the age of 14, and Asian race.[6] Mutations of NLRP7 OR KHDCL were found responsible for disruption of entire maternal imprinting gene expression. NLRP7 participates in the development of hydatidiform mole through inflammatory pathways, which could be used as a new targeted treatment and closely associated with the incidence of familial aggregation of hydatidiform moles.[7] Bruchim et al.[8] agreed that CHMCF occurred after induction of ovulation by clomiphene or HMG/HCG therapy. Another assumption is that forced ovulation of more than one ovum by induction treatment increases the rate of a nuclear empty ovum[9] and increases the risk of abnormal fertilization. The prominent problem in these pregnancies conceived after ART is the evaluation regarding the chance of obtaining a normal child versus the risk of developing complications.

Stellar et al. noted a higher risk of developing PGTD (50%) in cases with twin molar pregnancies with coexistent fetus, when compared to singleton molar pregnancies and more commonly progress to metastatic disease.[10] PGTD requires multiple cycles of combination chemotherapy.[11] Observation made in some studies is that PGTD was more often seen in those hydatidiform mole coexistent with a twin live fetus (HMTF) with maternal complications.[12] Our literature review showed no significant difference between maternal complications and the development of PGTD. Niemann et al.'s study analyzed 270 histologically and genetically confirmed complete hydatidiform mole with co-existing fetus (CHMF) to evaluate the risk of persistent gestational trophoblastic disease (PGTD), and other obstetrical complications, showed no differences between singleton and twin molar pregnancies.[4] According to Bristow et al., advanced gestational age is not an independent risk factor for the development of PGTD.[11] Some pregnancies with a CMCF develop malignancy irrespective of the time. Thus, the pregnancy is terminated even when intervention occurs in early pregnancy since the risk of malignancy persists. In our literature review, the mean gestational age at termination was 20.58 in patients who developed PGTD. There was no significant difference in the risk of developing PGTD in patients undergoing termination of pregnancy as well as the patients allowed to continue the pregnancy (P = 0.17).

The overall incidence of PGTD in patients with HMTF was 30.6%, and the rate increased to 50% in patients with CHMTF.[12] In our literature review, patients with hydatidiform mole with a coexistent fetus after ART, the incidence of developing PGTD was 42.85% which is similar to the earlier studies. Despite no increased risk of PGTD, the incidence of live birth rate was 39.28%. In our first case, pregnancy was continued and delivered a term live infant. The second case was aborted at 16 weeks' gestation due to maternal complications. These two patients needed chemotherapy due to PGTD. The rarity of this condition poses several diagnostic and management challenges, especially conceiving after ART the decision of termination for such couples.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


  Conclusion Top


Our results suggest that patients with hydatidiform mole and coexistent live fetus may be allowed to continue the pregnancy, provided the fetus has a normal karyotype, and the maternal complications are controlled along with postmolar follow-up. Further, a larger series of patient data is required to assess the risk of continuation of pregnancy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Chiang J, Berek J, Goff B, Falk S. Gestational trophoblastic disease: Epidemiology, clinical manifestations and diagnosis. UpToDate; 2011.  Back to cited text no. 1
    
2.
Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet 2010;376:717-29.  Back to cited text no. 2
    
3.
Sebire NJ, Foskett M, Paradinas FJ, Fisher RA, Francis RJ, Short D, et al. Outcome of twin pregnancies with complete hydatidiform mole and healthy co-twin. Lancet 2002;359:2165-6.  Back to cited text no. 3
    
4.
Niemann I, Sunde L, Petersen LK. Evaluation of the risk of persistent trophoblastic disease after twin pregnancy with diploid hydatidiform mole and coexisting normal fetus. Am J Obstet Gynecol 2007;197:5.e1-5.  Back to cited text no. 4
    
5.
Oliveira SA, Sampaio LA, Klevestona T, Filho VOAM. Twin pregnancy with complete hydatidiform mole and live fetus after egg donation and in vitro fertilization: case repor. Reprod Clim 2013. Article in press.  Back to cited text no. 5
    
6.
Jennifer D, Mc Cartie RT Complete twin molar pregnancy. JDMS 2002;18:100-3.  Back to cited text no. 6
    
7.
Zheng L, FengfengCai, Fan F, He J, Yan H, Bai C, et al. Complete hydatidiform mole coexisting live fetus in a twin pregnancy. Int J Clin Exp Med 2019;12:6238-43.  Back to cited text no. 7
    
8.
Bruchim I, Kidron D, Amiel A, Altaras M, Fejgin MD. Complete hydatidiform mole and a coexistent viable fetus: Report of two cases and review of the literature. Gynecol Oncol 2000;77:197-202.  Back to cited text no. 8
    
9.
Zilberman Sharon N, Melcer Y, Maymon R. Is a complete hydatidiform mole and a co-existing normal fetus an iatrogenic effect? Isr Med Assoc J 2019;21:653-7.  Back to cited text no. 9
    
10.
Steller MA, Genest DR, Bernstein MR, Lage JM, Goldstein DP, Berkowitz RS. Natural history of twin pregnancy with complete hydatidiform mole and coexisting fetus. Obstet Gynecol 1994;83:35-42.  Back to cited text no. 10
    
11.
Bristow RE, Shumway JB, Khouzami AN, Witter FR. Complete hydatidiform mole and surviving coexistent twin. Obstet Gynecol Surv 1996;51:705-9.  Back to cited text no. 11
    
12.
Matsui H, Sekiya S, Hando T, Wake N, Tomoda Y. Hydatidiform mole coexistent with a twin live fetus: A national collaborative study in Japan. Hum Reprod 2000;15:608-11.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

 
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