case presentation of molar pregnancy

Hydatidiform mole: Recognition and management

Molar pregnancies may be associated with serious morbidity so prompt diagnosis, appropriate management, and follow-up are essential.

Figures 3A, 3B, 3C

Hydatidiform mole is an abnormal pregnancy characterized by varying degrees of trophoblastic proliferation (both cytotrophoblast and syncytiotrophoblast) and vesicular swelling of placental villi associated with an absent or abnormal fetus/embryo. Two types of hydatidiform mole, complete and partial, have been described based on both morphologic and cytogenetic criteria (Table 1). 1,2

Epidemiology

Epidemiologic studies have reported wide regional variations in the incidence of molar pregnancies. Estimates from studies in North America, Europe, Australia and New Zealand have shown incidence rates ranging from 0.57-1.1 per 1000 pregnancies, whereas studies in Southeast Asia and Japan have suggested an incidence rate as high as 2.0 per 1000 pregnancies. These reported differences may be related to lack of standardization of data collection and reporting rather than true incidence differences. However, socioeconomic status and diet rather than genetic or cultural factors may also contribute to these reported differences in incidence rates. Declining incidence of molar pregnancies in Asia has been attributed to increasing western diet and improved standard of living. The overall incidence of molar pregnancies in the United States and Europe is about 1/1000 pregnancies for both complete and partial moles. 1,2

Several potential etiologic risk factors for development of molar pregnancy have been evaluated (Table 2). 3 For complete hydatidiform moles, two well-established risk factors have emerged: (1) extremes of maternal age; and (2) prior molar pregnancy. Both advanced and very young maternal age have consistently correlated with higher rates of complete mole. Compared to risk in women aged 21 to 35 years, risk of complete mole is 1.9 times higher for women both < 21 years and > 35 years and 7.5 times higher for women > 40 years, including 1 in 3 pregnancies for women > 50 years. These observations suggest that ova of very young or older women are predisposed to abnormal fertilization events that lead to complete hydatidiform moles. Prior complete molar pregnancy increases risk of developing a subsequent complete molar pregnancy. 

Risk of a repeat molar pregnancy after one mole is approximately 1%, about 10 to 20 times the risk for the general population, while after two moles, the risk of a third mole is 15% to 20%. History of prior spontaneous abortion also appears to increase risk of a molar pregnancy (both complete and partial) 2- to 3-fold compared to women without a history of prior miscarriage. Dietary deficiency of β-carotene and animal fat has been linked to an increase in complete moles. There appears to be a possible increased risk of molar pregnancy (partial and complete) with a history of oral contraceptive use, while ovulation induction regimens may be associated with an increase in twin pregnancies consisting of a normal fetus(es) and a complete mole. 

While several definite etiologic risk factors have been identified for complete moles, the epidemiologic characteristics of partial moles differ and are less well defined. Importantly, the association between maternal age and complete molar pregnancies is not seen in women with partial molar pregnancies. Furthermore, partial molar pregnancies are more common in women with a history of irregular menses, miscarriage, and oral contraceptive use for > 4 years, but are not associated with ethnicity, ovulation induction, or dietary factors. 

Complete hydatidiform moles usually arise when an ovum without maternal chromosomes is fertilized by one sperm which then duplicates its DNA, resulting in a 46, XX androgenic karyotype in which all the chromosomes are paternally derived. About 10% of complete moles are 46, XY or 46, XX arising from fertilization of an “empty ovum” by two sperm. Bipaternal diploid complete moles are associated with a maternal autosomal-recessive missense gene mutation, most commonly NLRP7 on chromosome 19q, which results in repetitive molar pregnancies. Partial hydatidiform moles have a triploid karyotype, usually 69, XXY, resulting from dispermic fertilization of an apparently normal ovum (Figure 1). 2

Complete hydatidiform moles undergo early and uniform hydatid enlargement of villi in the absence of an ascertainable fetus or embryo, the trophoblast is consistently hyperplastic with varying degrees of atypia, and villous capillaries are absent. Partial hydatidiform moles demonstrate identifiable fetal or embryonic tissue, chorionic villi of varying size and shape with focal edema, scalloping and prominent stromal inclusions, a functioning villous circulation, as well as focal trophoblastic hyperplasia with only mild atypia. Immunohistochemical staining for p57 (a parentally imprinted, maternally expressed gene) may be useful for differentiating a positive partial mole from a negative complete mole, but cannot be used to distinguish a partial mole from a nonmolar abortus both of which are positive. 4-6

Clinical presentation  

Complete hydatidiform moles most commonly present with vaginal bleeding, usually occurring at 6 to 16 weeks of gestation in 90% of cases. The other classical clinical signs and symptoms, such as uterine enlargement greater than expected for gestational dates (28%), hyperemesis (8%), and toxemia, hyperthyroidism, and trophoblastic embolization (< 1%), occur less frequently in more recent years due to earlier diagnosis as a result of widespread use of ultrasonography and accurate tests for human chorionic gonadotrophin (hCG). Bilateral theca lutein cyst enlargement of the ovaries occurs in approximately 15% of cases, hCG levels are often > 100,000 mIU/mL, and fetal heart sounds are absent. 7,8

Partial hydatidiform moles do not have the same presenting features as complete moles. Although the main presenting symptom is also vaginal bleeding, which occurs in about 75% of patients, excessive uterine enlargement, hyperemesis, pregnancy-induced hypertension, hyperthyroidism, and theca lutein cysts develop infrequently. Fewer than 10% have hCG levels > 100,000 mIU/mL. More than 90% of patients with partial moles have symptoms and ultrasound findings consistent with an incomplete or missed abortion, and the diagnosis is usually made only after histologic examination of uterine curettage specimens. 9

Ultrasonography plays a critical role in the diagnosis of both complete and partial molar pregnancy, and it has virtually replaced all other means of preoperative diagnosis. Because the chorionic villi of complete moles exhibit diffuse hydropic swelling, a characteristic vesicular ultrasonographic pattern can be observed consisting of multiple echoes (holes) within the placental mass and usually no fetus (Figure 2). Ultrasonography may also facilitate early diagnosis of a partial mole by demonstrating focal cystic spaces within the placenta and an increase in the transverse diameter of the gestational sac. 12

hCG is a disease-specific tumor marker produced by the trophoblast of hydatidiform moles and gestational trophoblastic neoplasms as well as normal pregnancy. Hydatidiform moles are commonly associated with markedly elevated hCG levels above those of normal pregnancy. Approximately 50% of complete moles have pre-evacuation hCG levels > 100,000 mIU/mL. However, a single hCG level is seldom helpful in differentiating a compete mole from another type of pregnancy. Partial moles, on the other hand, are most often not associated with such elevated hCG levels, as noted previously. 13

Despite earlier diagnosis of complete moles resulting in fewer complications, there has not been a simultaneous reduction in incidence of postmolar gestational trophoblastic neoplasia (GTN). 

Once the diagnosis of molar pregnancy is suspected based on history, physical examination, hCG level, and ultrasound findings, the patient should be evaluated for the presence of medical complications (anemia, preeclampsia, hyperthyroidism), which may need to be corrected. Basic laboratory tests should include complete blood count, comprehensive metabolic panel, thyroid function test, urinalysis, and chest x-ray, as well as blood type and screen with cross match if anemic or uterus ≥ 16-week gestational size. An electrocardiogram and coagulation profile may also be indicated. Once the patient is determined to be hemodynamically stable, the most appropriate method of molar evacuation should be decided upon. 1, 2,14

Suction evacuation and curettage is the preferred method of evacuation of a hydatidiform mole, independent of uterine size, for patients who wish to maintain their fertility. After anesthesia is achieved, the cervix is dilated to allow a 12- to 14-mm suction cannula to pass into the lower uterine segment and then rotated as the intrauterine contents are removed, preferably under ultrasound guidance. Suction evacuation should be followed by gentle sharp curettage. Uterotonic drugs should be started after initiation of evacuation of the uterus, although oxytocin receptors may be absent. Because risk of excessive bleeding increases with uterine size, 2 units of blood should be immediately available when the uterus is ≥ 16-week gestational size. Attention to blood and crystalloid replacement decreases pulmonary complications. It is clear that with judicious use of appropriate equipment, access to blood products, careful intraoperative monitoring, and early anticipation of complications, patient outcomes improve. Patients who are Rh-negative should receive Rho(D) immune globulin at the time of evacuation, as Rh D factor is expressed on trophoblastic cells. 

Hysterectomy is an alternative to suction curettage in patients who do not wish to preserve fertility or are older and at increased risk for development of postmolar GTN. The adnexa may be left intact even in the presence of theca lutein cysts. In addition to evacuating the molar pregnancy, hysterectomy provides permanent sterilization and eliminates risk of local myometrial invasion as a cause of persistent disease. Because of the potential for metastatic disease even after hysterectomy, risk of postmolar GTN still remains at 3% to 5%, thereby requiring continued hCG follow up. 

Medical induction of labor and hysterotomy are not recommended for molar evacuation. These methods increase maternal morbidity, such as blood loss, incomplete evacuation requiring curettage, and the requirement for cesarean delivery in subsequent pregnancies. They also increase trophoblastic dissemination and the development of postmolar GTN requiring chemotherapy. 

Prophylactic chemotherapy at the time or immediately after evacuation of a molar pregnancy is associated with a reduction in incidence of postmolar GTN from approximately 15% to 20% down to 3% to 8%. 15 Use of prophylactic chemotherapy should be limited, however, to special situations in which risk of postmolar GTN is much greater than normal (age > 40 years, hCG > 100,000 mIU/mL, excessive uterine enlargement, theca lutein cysts > 6 cm, medical complications) and/or when adequate hCG follow-up is unavailable or unreliable. Essentially all patients who are followed with serial hCG testing after molar evacuation and are found to have persistent GTN can be cured with appropriate chemotherapy. 

Twin pregnancy consisting of a complete mole and a coexisting normal fetus is estimated to occur once in every 22,000 to 100,000 pregnancies (Figure 3). It must be distinguished from a partial mole (triploid pregnancy with fetus). The diagnosis can usually be established by ultrasound, but cytogenetics may be used to differentiate between chromosomally normal, potentially viable fetuses and triploid nonviable fetuses. Patients with a normal fetus/complete mole twin pregnancy should be cautioned that they may be at increased risk for hemorrhage, medical complications, and development of persistent GTN. Suction evacuation and curettage in the operating room under ultrasound guidance is recommended for desired pregnancy termination, bleeding, or medical complications. However, up to 40% of these pregnancies will result in normal viable births if allowed to continue. 16,17

After evacuation of a hydatidiform mole, follow-up is essential to detect trophoblastic sequelae (invasive mole and choriocarcinoma), which develop in approximately 15% to 20% of patients with complete mole and 1% to 5% with partial mole. 1,2,14,18 Clinical findings of prompt uterine involution, ovarian cyst regression, and cessation of bleeding are all reassuring signs, however, definitive follow-up requires serial serum hCG measurements every 1 to 2 weeks until three consecutive tests show normal hCG levels, after which hCG levels should be determined at 3-month intervals for  6 months after the spontaneous return to normal. Contraception is recommended during the follow-up period for 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, and do not increase the risk of postmolar GTN. Indications for treatment of postmolar GTN are: plateauing hCG levels x4 values over 3 weeks, rising hCG levels ≥ 10% x three values over 2 weeks, persistently elevated hCG levels 6 months after evacuation, a histopathologic diagnosis of choriocarcinoma or intermediate trophoblastic tumor, or detection of metastases. 19-21 In all future pregnancies, pathologic examination of the placenta or other products of conception as well as determination of a 6-week postpartum hCG level are recommended. 

Disclosures:

The author reports no potential conflicts of interest with regard to this artic

References:

• Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol. 2010;203:531-539.
• Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet. 2010;376:717-729
• Strohl AE, Lurain JR. Clinical epidemiology of gestational trophoblastic disease. Curr Obstet Gynecol. Rep 2014;3 40-43
• Szulman AE, Surti U. The syndromes of hydatidiform mole. I: cytogenetic and morphologic correlations. Am J Obstet Gynecol. 1978;131:665-671.
• Szulman AE, Surti U. The syndromes of hydatidiform mole. II: morphologic evolution of the complete and partial mole. Am J Obstet Gynecol. 1978;132:20-27.
• Castrillon DH, Sun D, Weremowicz S, et al. Discrimination of complete hydatidiform mole from its mimics by immunohistochemistry of paternally imprinted gene product p57K1P2. Am J Surg Pathol. 2001;25:1225-1230.
• Soto-Wright V, Bernstein MR, Goldstein DP, et al. The changing clinical presentation of complete molar pregnancy. Obstet Gynecol. 1995;86:775-779.
• Hou JL, Wan XR, Xiang Y, et al. Changes in clinical features in hydatidiform mole: analysis of 113 cases. J Reprod Med. 2008:53:629-633.
• Berkowitz RS, Goldstein DP, Bernstein MR. Natural history of partial molar pregnancy. Obstet Gynecol. 1985;66:677-681.
• Santos-Ramos R, Forney JP, Schwarz BE. Sonographic findings and clinical correlations in molar pregnancy. Obstet Gynecol. 1980;56:186-192.
• Benson CB, Genset DR, Bernstein MR, et al. Sonographic appearance of first trimester complete hydatidiform mole. Obstet Gynecol. 1989;73:414-418.
• Fine C, Bundy AL, Berkowitz RS, et al. Sonographic diagnosis of partial hydatidiform mole. Obstet Gynecol. 1989;73:414-418.
• Berkowitz RS, Ozturk M, Goldstein DP, et al. Human chorionic gonadotropin and free subunits’ serum levels in patients with partial and complete hydatidiform moles. Obstet Gynecol. 1989;74:212-216.
• Berkowitz RS, Goldstein DP. Clinical practice. Molar pregnancy. N Engl J Med. 2009;360:1639-1645.
• Wang Q, Fu J, Hu L, et al. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia. Cochrane Database Syst Rev. 2017;9:CD 007289.
• Sebire NJ, Foskett M, Paradinas FJ, et al. Outcome of twin pregnancies with complete hydatidiform mole and healthy co-twin. Lancet. 2002;359:2165-2166.
• Lin LH, Maesta I, Braga A, et al. Multiple pregnancies with complete mole and coexisting normal fetus in North and South America: a retrospective multicenter cohort and literature review. Gynecol Oncol. 2017;145:88-95.
• Lurain JR, Brewer JI, Torok E, Halpern B. Natural history of hydatidiform mole after primary evacuation. Am J Obstet Gynecol. 1983;145:591-595.
• Ngan HYS, Bender H, Benedet JL, et al. Gestational trophoblastic neoplasia, FIGO staging and classification. Int J Gynecol Obstet. 2003;83:175-177.
• Lurain JR. Gestational trophoblastic disease. II: classification and management of gestational trophoblastic neoplasia. Am J Obstet Gynecol. 2011;204:11-18.
• NCCN Guidelines: gestational trophoblastic neoplasia, version 1. 2019, 2018.

Evaluating second-stage cesarean delivery’s link to preterm birth

Investigating the potential association between second-stage cesarean delivery and heightened preterm birth risk revealed significant findings amidst concerns of bias, urging further exploration.

S1E4: Dr. Kristina Adams-Waldorf: Pandemics, pathogens and perseverance

This episode of Pap Talk by Contemporary OB/GYN features an interview with Dr. Kristina Adams-Waldorf, Professor in the Department of Obstetrics and Gynecology and Adjunct Professor in Global Health at the University of Washington (UW) School of Medicine in Seattle.

Study reveals link between opioid dosage and spontaneous preterm birth risk

Recent research highlighted an association between the total dose of prescribed opioids during pregnancy and the heightened risk of spontaneous preterm birth, emphasizing the need for judicious opioid use in pain management for expectant mothers.

S1E3: Dr. Emily S. Miller: Placental pathology and MVM evidence

This episode of Pap Talk by Contemporary OB/GYN features an interview with Dr. Emily S. Miller, with Northwestern Medicine in Chicago.

Contemporary OB/GYN week in review: abortion, cesarean delivery, and more

Review some of the top stories from the Contemporary OB/GYN website over the last week, and catch up on anything you may have missed.

Assessing low-risk cesarean delivery rates: Florida's 4-year study insights

A comprehensive study reveals variations in monitoring low-risk cesarean delivery rates across 5 metrics, emphasizing the significance of timely and accurate assessment from birth certificate data.

2 Commerce Drive Cranbury, NJ 08512

609-716-7777

Advertisement

Molar Pregnancy: Epidemiology, Diagnosis, Management, Surveillance

• Family Planning (A Roe and S Sonalkar, Section Editors)
• Published: 19 February 2022
• Volume 11 , pages 133–141, ( 2022 )

Cite this article

• Alice J. Darling   ORCID: orcid.org/0000-0002-4708-9247 1 ,
• Benjamin B. Albright 2 ,
• Kyle C. Strickland 3 &
• Brittany A. Davidson 2  

463 Accesses

Explore all metrics

Purpose of Review

This review describes recommendations for the diagnosis and management of molar pregnancy, with focus on emerging evidence in recent years, particularly as it pertains to nuances of diagnosis, risk stratification, and surveillance of post-molar malignant trophoblastic disease.

Recent Findings

Topics discussed include advances in histopathologic diagnosis of molar pregnancy to standardize analysis, most recent estimations of post-molar pregnancy malignancy, and updated surveillance guidelines.

Hydatidiform molar pregnancy, resulting from an abnormal fertilization event, is the proliferation of abnormal pregnancy tissue with malignant potential. With increased availability of first trimester ultrasound, early detection of molar pregnancy has increased. While challenging to diagnose radiologically and histologically at early stages, standardization of tissue analysis allows improved detection and increased accuracy of incidence estimate for both complete and partial molar pregnancy. Treatment of molar pregnancy requires evacuation of tissue. Prophylactic chemotherapy or repeat curettage have been explored but not favored. As new molecular markers are sought, our ability to predict malignant transformation following molar pregnancies will allow for more streamlined surveillance. Recent data support a reduction in the length of surveillance following normalization of human chorionic gonadotropin levels after evacuation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price includes VAT (Russian Federation)

Instant access to the full article PDF.

Rent this article via DeepDyve

Institutional subscriptions

Similar content being viewed by others

Recurrent Molar Pregnancy

Clinicopathological Study of Gestational Trophoblastic Disease (GTD) in a Tertiary Care Hospital

Sairindri Sahoo, Indira Palo, … Susanta Kumar Behera

Evaluation of a routine second curettage for hydatidiform mole: a cohort study

Eiko Yamamoto, Kimihiro Nishino, … Fumitaka Kikkawa

Papers of particular interest, published recently, have been highlighted as:

• of importance.

• Albright BB, Shorter JM, Mastroyannis SA, Ko EM, Schreiber CA, Sonalkar S. Gestational trophoblastic neoplasia after human chorionic gonadotropin normalization following molar pregnancy: a systematic review and meta-analysis. Obstet Gynecol. 2020;135(1):12–23. https://doi.org/10.1097/AOG.0000000000003566 . A systematic review and meta-analysis of post-molar gestational trophoblastic neoplasia incidence. This review found a very low (64/18,357, 0.35%, 95% CI 0.27-0.45%) cumulative incidence of GTN development after hCG normalization following a complete molar pregnancy. This rate was even lower for partial moles (5/14,864, 0.03%, 95% CI 0.01-0.08%) .

Article   Google Scholar  

Seckl MJ, Sebire NJ, Fisher RA, Golfier F, Massuger L, Sessa C. Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 2013;24(6):vi39–50. https://doi.org/10.1093/annonc/mdt345 .

• Ngan HYS, Seckl MJ, Berkowitz RS, Xiang Y, Golfier F, Sekharan PK, et al. Update on the diagnosis and management of gestational trophoblastic disease. Int J Gynecol Obstet. 2018;143(S2):79–85. https://doi.org/10.1002/ijgo.12615 . FIGO Cancer Report of 2018 reviewing Gestational Trophoblastic Disease. Includes updated FIGO guidelines-most notably removing elevated hCG at ≥6 months after uterine evacuation from GTN diagnostic criteria and specifying hCG followup intervals including reduced surveillance length after partial molar pregnancy .

Soper JT. Gestational Trophoblastic Disease: Current Evaluation and Management. Obstet Gynecol. 2021;137(2):355–70. https://doi.org/10.1097/aog.0000000000004240 .

Brown J, Naumann RW, Seckl MJ, Schink J. 15 years of progress in gestational trophoblastic disease: scoring, standardization, and salvage. Gynecol Oncol. 2017;144(1):200–7. https://doi.org/10.1016/J.YGYNO.2016.08.330 .

Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol. 2010;203(6):531–9. https://doi.org/10.1016/J.AJOG.2010.06.073 .

Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. The Lancet. 2010;376(9742):717–29. https://doi.org/10.1016/S0140-6736(10)60280-2 .

Berkowitz RS, Goldstein DP. Current management of gestational trophoblastic diseases. Gynecol Oncol. 2009;112(3):654–62. https://doi.org/10.1016/J.YGYNO.2008.09.005 .

Article   CAS   Google Scholar  

Maisenbacher MK, Merrion K, Kutteh WH. Single-nucleotide polymorphism microarray detects molar pregnancies in 3% of miscarriages. Fertil Steril. 2019;112(4):700–6. https://doi.org/10.1016/j.fertnstert.2019.06.015 .

Cozette C, Scheffler F, Lombart M, Massardier J, Bolze PA, Hajri T, et al. Pregnancy after oocyte donation in a patient with NLRP7 gene mutations and recurrent molar hydatidiform pregnancies. J Assist Reprod Genet. 2020;37(9):2273–7. https://doi.org/10.1007/s10815-020-01861-z .

Eagles N, Sebire NJ, Short D, Savage PM, Seckl MJ, Fisher RA. Risk of recurrent molar pregnancies following complete and partial hydatidiform moles. Hum Reprod. 2015;30(9):2055–63. https://doi.org/10.1093/humrep/dev169 .

Gockley AA, Melamed A, Joseph NT, Clapp M, Sun SY, Goldstein DP, et al. The effect of adolescence and advanced maternal age on the incidence of complete and partial molar pregnancy. Gynecol Oncol. 2016;140(3):470–3. https://doi.org/10.1016/J.YGYNO.2016.01.005 .

Savage PM, Sita-Lumsden A, Dickson S, Iyer R, Everard J, Coleman R, et al. The relationship of maternal age to molar pregnancy incidence, risks for chemotherapy and subsequent pregnancy outcome. J Obstet Gynaecol. 2013;33(4):406–11. https://doi.org/10.3109/01443615.2013.771159 .

Sebire NJ, Foskett M, Fisher RA, Rees H, Seckl M, Newlands E. Risk of partial and complete hydatidiform molar pregnancy in relation to maternal age. BJOG Int J Obstet Gynaecol. 2002;109(1):99–102. https://doi.org/10.1111/j.1471-0528.2002.t01-1-01037.x .

Sato A, Usui H, Shozu M. ABO blood type compatibility is not a risk factor for gestational trophoblastic neoplasia development from androgenetic complete hydatidiform moles. Am J Reprod Immunol. 2020;83(6):e13237. https://doi.org/10.1111/aji.13237 .

Shamshiri Milani H, Abdollahi M, Torbati S, Asbaghi T, Azargashb E. Risk Factors for hydatidiform mole: is husband’s job a major risk factor?. Asian Pac J Cancer Prev. 2017;18(10):2657–62. https://doi.org/10.22034/apjcp.2017.18.10.2657 .

Berkowitz RS, Bernstein MR, Harlow BL, Rice LW, Lage JM, Goldstein DP, et al. Case-control study of risk factors for partial molar pregnancy. Am J Obstet Gynecol. 1995;173(3 Pt 1):788–94. https://doi.org/10.1016/0002-9378(95)90342-9 .

Melamed A, Gockley AA, Joseph NT, Sun SY, Clapp MA, Goldstein DP, et al. Effect of race/ethnicity on risk of complete and partial molar pregnancy after adjustment for age. Gynecol Oncol. 2016;143(1):73–6. https://doi.org/10.1016/j.ygyno.2016.07.117 .

Sundvall L, Lund H, Niemann I, Jensen UB, Bolund L, Sunde L. Tetraploidy in hydatidiform moles. Hum Reprod. 2013;28(7):2010–20. https://doi.org/10.1093/humrep/det132 .

Sebire NJ, Savage PM, Seckl MJ, Fisher RA. Histopathological features of biparental complete hydatidiform moles in women with NLRP7 mutations. Placenta. 2013;34(1):50–6. https://doi.org/10.1016/j.placenta.2012.11.005 .

Fisher RA, Hodges MD, Newlands ES. Familial recurrent hydatidiform mole: a review. J Reprod Med. 2004;49(8):595–601.

Google Scholar  

King JR, Wilson ML, Hetey S, Kiraly P, Matsuo K, Castaneda AV et al. Dysregulation of placental functions and immune pathways in complete hydatidiform moles. Int J Mol Sci. 2019;20(20). https://doi.org/10.3390/ijms20204999 .

Fisher RA, Maher GJ. Genetics of gestational trophoblastic disease. Best Pract Res Clin Obstet Gynaecol. 2021;74:29–41. https://doi.org/10.1016/j.bpobgyn.2021.01.004 .

Soellner L, Begemann M, Degenhardt F, Geipel A, Eggermann T, Mangold E. Maternal heterozygous NLRP7 variant results in recurrent reproductive failure and imprinting disturbances in the offspring. Eur J Hum Genet. 2017;25(8):924–9. https://doi.org/10.1038/ejhg.2017.94 .

Sun SY, Melamed A, Joseph NT, Gockley AA, Goldstein DP, Bernstein MR, et al. Clinical presentation of complete hydatidiform mole and partial hydatidiform mole at a regional trophoblastic disease center in the United States over the past 2 decades. Int J Gynecol Cancer. 2016;26(2):367–70. https://doi.org/10.1097/IGC.0000000000000608 .

Sun SY, Melamed A, Goldstein DP, Bernstein MR, Horowitz NS, Moron AF, et al. Changing presentation of complete hydatidiform mole at the New England Trophoblastic Disease Center over the past three decades: does early diagnosis alter risk for gestational trophoblastic neoplasia?. Gynecol Oncol. 2015;138(1):46–9. https://doi.org/10.1016/J.YGYNO.2015.05.002 .

Winder AD, Mora AS, Berry E, Lurain JR. The “hook effect” causing a negative pregnancy test in a patient with an advanced molar pregnancy. Gynecol Oncol Rep. 2017;21:34–6. https://doi.org/10.1016/j.gore.2017.06.008 .

Li P, Koch CD, El-Khoury JM. Perimenopausal woman with elevated serum hCG and abdominal pain. Clin Chim Acta. 2021;522:141–3. https://doi.org/10.1016/j.cca.2021.08.018 .

Ross JA, Unipan A, Clarke J, Magee C, Johns J. Ultrasound diagnosis of molar pregnancy. Ultrasound. 2018;26(3):153–9. https://doi.org/10.1177/1742271x17748514 .

Savage JL, Maturen KE, Mowers EL, Pasque KB, Wasnik AP, Dalton VK, et al. Sonographic diagnosis of partial versus complete molar pregnancy: a reappraisal. J Clin Ultrasound. 2017;45(2):72–8. https://doi.org/10.1002/jcu.22410 .

Ronnett BM. Hydatidiform moles: ancillary techniques to refine diagnosis. Arch Pathol Lab Med. 2018;142(12):1485–502. https://doi.org/10.5858/arpa.2018-0226-RA .

Hui P, Buza N, Murphy KM, Ronnett BM. Hydatidiform moles: genetic basis and precision diagnosis. Annu Rev Pathol. 2017;12:449–85. https://doi.org/10.1146/annurev-pathol-052016-100237 .

Madi JM, Braga A, Paganella MP, Litvin IE, Wendland EM. Accuracy of p57(KIP)(2) compared with genotyping to diagnose complete hydatidiform mole: a systematic review and meta-analysis. BJOG. 2018;125(10):1226–33. https://doi.org/10.1111/1471-0528.15289 .

Zheng XZ, Qin XY, Chen SW, Wang P, Zhan Y, Zhong PP, et al. Heterozygous/dispermic complete mole confers a significantly higher risk for post-molar gestational trophoblastic disease. Mod Pathol. 2020;33(10):1979–88. https://doi.org/10.1038/s41379-020-0566-4 .

Lin LH, Maestá I, St Laurent JD, Hasselblatt KT, Horowitz NS, Goldstein DP, et al. Distinct microRNA profiles for complete hydatidiform moles at risk of malignant progression. Am J Obstet Gynecol. 2021;224(4):372.e1-e30. https://doi.org/10.1016/j.ajog.2020.09.048 .

Braga A, Maestá I, Rocha Soares R, Elias KM, Custódio Domingues MA, Barbisan LF, et al. Apoptotic index for prediction of postmolar gestational trophoblastic neoplasia. Am J Obstet Gynecol. 2016;215(3):336.e1-.e12. https://doi.org/10.1016/j.ajog.2016.04.010 .

Padrón L, Rezende Filho J, Amim Junior J, Sun SY, Charry RC, Maestá I, et al. Manual compared with electric vacuum aspiration for treatment of molar pregnancy. Obstet Gynecol. 2018;1-. https://doi.org/10.1097/AOG.0000000000002522 .

Curry SL, Hammond CB, Tyrey L, Creasman WT, Parker RT. Hydatidiform mole: diagnosis, management, and long-term followup of 347 patients. Obstet Gynecol. 1975;45(1):1–8.

CAS   Google Scholar  

• Zhao P, Lu Y, Huang W, Tong B, Lu W. Total hysterectomy versus uterine evacuation for preventing post-molar gestational trophoblastic neoplasia in patients who are at least 40 years old: a systematic review and meta-analysis. BMC Cancer. 2019;19(1):13. https://doi.org/10.1186/s12885-018-5168-x . A systematic review and meta-analysis which demonstrated a risk reduction in post-molar GTN of more than 80% in patients ≥40 years old following hysterectomy compared to those receiving uterine evacuations for molar pregnancy treatment .

Giorgione V, Bergamini A, Cioffi R, Pella F, Rabaiotti E, Petrone M, et al. Role of surgery in the management of hydatidiform mole in elderly patients: a single-center clinical experience. Int J Gynecol Cancer. 2017;27(3):550–3. https://doi.org/10.1097/igc.0000000000000903 .

Eysbouts YK, Massuger L, IntHout J, Lok CAR, Sweep F, Ottevanger PB. The added value of hysterectomy in the management of gestational trophoblastic neoplasia. Gynecol Oncol. 2017;145(3):536–42. https://doi.org/10.1016/j.ygyno.2017.03.018 .

Yamamoto E, Nishino K, Niimi K, Watanabe E, Oda Y, Ino K, et al. Evaluation of a routine second curettage for hydatidiform mole: a cohort study. Int J Clin Oncol. 2020;25(6):1178–86. https://doi.org/10.1007/s10147-020-01640-x .

Yamamoto E, Trinh TD, Sekiya Y, Tamakoshi K, Nguyen XP, Nishino K, et al. The management of hydatidiform mole using prophylactic chemotherapy and hysterectomy for high-risk patients decreased the incidence of gestational trophoblastic neoplasia in Vietnam: a retrospective observational study. Nagoya J Med Sci. 2020;82(2):183–91. https://doi.org/10.18999/nagjms.82.2.183 .

Wang Q, Fu J, Hu L, Fang F, Xie L, Chen H, et al. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia. Cochrane Database of Syst Rev. 2017;9:CD007289-CD. https://doi.org/10.1002/14651858.CD007289.pub3 .

Jiao LZ, Wang YP, Jiang JY, Zhang WQ, Wang XY, Zhu CG, et al. Clinical significance of centralized surveillance of hydatidiform mole. Zhonghua Fu Chan Ke Za Zhi. 2018;53(6):390–5. https://doi.org/10.3760/cma.j.issn.0529-567x.2018.06.006 .

Braga A, Biscaro A, do Amaral Giordani JM, Viggiano M, Elias KM, Berkowitz RS, et al. Does a human chorionic gonadotropin level of over 20,000 IU/L four weeks after uterine evacuation for complete hydatidiform mole constitute an indication for chemotherapy for gestational trophoblastic neoplasia?. Eur J Obstet Gynecol Reprod Biol. 2018;223:50–5. https://doi.org/10.1016/j.ejogrb.2018.02.001 .

Ngu SF, Ngan HYS. Surgery including fertility-sparing treatment of GTD. Best Pract Res Clin Obstet Gynaecol. 2021;74:97–108. https://doi.org/10.1016/j.bpobgyn.2020.10.005 .

Zilberman Sharon N, Maymon R, Melcer Y, Jauniaux E. Obstetric outcomes of twin pregnancies presenting with a complete hydatidiform mole and coexistent normal fetus: a systematic review and meta-analysis. BJOG. 2020;127(12):1450–7. https://doi.org/10.1111/1471-0528.16283 .

Lin LH, Maestá I, Braga A, Sun SY, Fushida K, Francisco RPV, et al. Multiple pregnancies with complete mole and coexisting normal fetus in North and South America: A retrospective multicenter cohort and literature review. Gynecol Oncol. 2017;145(1):88–95. https://doi.org/10.1016/j.ygyno.2017.01.021 .

• Albright BB, Myers ER, Moss HA, Ko EM, Sonalkar S, Havrilesky LJ. Surveillance for gestational trophoblastic neoplasia following molar pregnancy: a cost-effectiveness analysis. Am J Obstet Gynecol. 2021. https://doi.org/10.1016/j.ajog.2021.05.031 . Cost-effectiveness analysis of post-molar GTN surveillance finding reduction or elimination of hCG surveillance would be cost effective and clinically reasonable given the rarity of malignant following hCG normalization. Additionally, found a single hCG test 3 months after uterine evacuation was a cost-effective alternative .

Massad LS, Abu-Rustum NR, Lee SS, Renta V. Poor compliance with postmolar surveillance and treatment protocols by indigent women. Obstet Gynecol. 2000;96(6):940–4. https://doi.org/10.1016/s0029-7844(00)01064-4 .

Blok LJ, Frijstein MM, Eysbouts YK, Custers J, Sweep F, Lok C, et al. The psychological impact of gestational trophoblastic disease: a prospective observational multicentre cohort study. BJOG. 2021. https://doi.org/10.1111/1471-0528.16849 .

Jewell EL, Aghajanian C, Montovano M, Lewin SN, Baser RE, Carter J. Association of ß-hCG surveillance with emotional, reproductive, and sexual health in women treated for gestational trophoblastic neoplasia. J Womens Health (Larchmt). 2018;27(3):387–93. https://doi.org/10.1089/jwh.2016.6208 .

Stafford L, McNally OM, Gibson P, Judd F. Long-term psychological morbidity, sexual functioning, and relationship outcomes in women with gestational trophoblastic disease. Int J Gynecol Cancer. 2011;21(7):1256–63. https://doi.org/10.1097/IGC.0b013e3182259c04 .

Coyle C, Short D, Jackson L, Sebire NJ, Kaur B, Harvey R, et al. What is the optimal duration of human chorionic gonadotrophin surveillance following evacuation of a molar pregnancy? A retrospective analysis on over 20,000 consecutive patients. Gynecol Oncol. 2018;148(2):254–7. https://doi.org/10.1016/j.ygyno.2017.12.008 .

Management of Gestational Trophoblastic Disease: Green-top Guideline No. 38 - June 2020. BJOG. 2021;128(3):e1-e27. https://doi.org/10.1111/1471-0528.16266 .

Horowitz NS, Eskander RN, Adelman MR, Burke W. Epidemiology, diagnosis, and treatment of gestational trophoblastic disease: a Society of Gynecologic Oncology evidenced-based review and recommendation. Gynecol Oncol. 2021;163(3):605–13. https://doi.org/10.1016/j.ygyno.2021.10.003 .

Lybol C, Sweep FC, Ottevanger PB, Massuger LF, Thomas CM. Linear regression of postevacuation serum human chorionic gonadotropin concentrations predicts postmolar gestational trophoblastic neoplasia. Int J Gynecol Cancer. 2013;23(6):1150–6. https://doi.org/10.1097/IGC.0b013e31829703ea .

Hardman S. Use of hormonal contraception after hydatidiform mole. BJOG Int J Obstet Gynaecol. 2016;123(8):1336. https://doi.org/10.1111/1471-0528.13691 .

Gaffield ME, Kapp N, Curtis KM. Combined oral contraceptive and intrauterine device use among women with gestational trophoblastic disease. Contraception. 2009;80(4):363–71. https://doi.org/10.1016/j.contraception.2009.03.022 .

Dantas PRS, Maestá I, Filho JR, Junior JA, Elias KM, Howoritz N, et al. Does hormonal contraception during molar pregnancy follow-up influence the risk and clinical aggressiveness of gestational trophoblastic neoplasia after controlling for risk factors? Gynecol Oncol. 2017;147(2):364–70. https://doi.org/10.1016/j.ygyno.2017.09.007 .

Braga A, Maestá I, Short D, Savage P, Harvey R, Seckl M. Hormonal contraceptive use before hCG remission does not increase the risk of gestational trophoblastic neoplasia following complete hydatidiform mole: a historical database review. BJOG Int J Obstet Gynaecol. 2016;123(8):1330–5. https://doi.org/10.1111/1471-0528.13617 .

Morbidity and Mortality Weekly Report: Classifications for Intrauterine Devices. Centers for Disease Control and Prevention. 2010. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr59e0528a6.htm . Accessed 25 Oct 2021.

Tuncer ZS, Bernstein MR, Goldstein DP, Lu KH, Berkowitz RS. Outcome of pregnancies occurring within 1 year of hydatidiform mole. Obstet Gynecol. 1999;94(4):588–90. https://doi.org/10.1016/S0029-7844(99)00395-6 .

Joneborg U, Coopmans L, van Trommel N, Seckl M, Lok CAR. Fertility and pregnancy outcome in gestational trophoblastic disease. Int J Gynecol Cancer. 2021;31(3):399–411. https://doi.org/10.1136/ijgc-2020-001784 .

Vargas R, Barroilhet LM, Esselen K, Diver E, Bernstein M, Goldstein DP, et al. Subsequent pregnancy outcomes after complete and partial molar pregnancy, recurrent molar pregnancy, and gestational trophoblastic neoplasia: an update from the New England Trophoblastic Disease Center. J Reprod Med. 2014;59(5–6):188–94.

Matsui H, Iitsuka Y, Suzuka K, Seki K, Sekiya S. Subsequent pregnancy outcome in patients with spontaneous resolution of HCG after evacuation of hydatidiform mole: comparison between complete and partial mole. Hum Reprod. 2001;16(6):1274–7. https://doi.org/10.1093/humrep/16.6.1274 .

Abu-Rustum NR, Yashar CM, Bean S, Bradley K, Campos SM, Chon HS, et al. Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019;17(11):1374–91. https://doi.org/10.6004/jnccn.2019.0053 .

Download references

Author information

Authors and affiliations.

Department of Obstetrics & Gynecology, Duke University, Durham, NC, USA

Alice J. Darling

Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Duke University, Durham, NC, USA

Benjamin B. Albright & Brittany A. Davidson

Department of Pathology, Duke University, Durham, NC, USA

Kyle C. Strickland

You can also search for this author in PubMed   Google Scholar

Contributions

AD: Project design, literature review, manuscript draft, critical revision, final approval. BA: Project conception and design, literature review, critical revision, final approval. KS: Collecting and preparing specimens for manuscript figure, critical revision, final approval. BD: Project conception and design, literature review, critical revision, final approval.

Ethics declarations

Ethics approval.

Not applicable, this article does not contain any studies with human or animal subjects performed by any of the authors.

Consent to Participate

Not applicable.

Consent for Publication

Conflict of interest.

The authors declare no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Family Planning

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Darling, A.J., Albright, B.B., Strickland, K.C. et al. Molar Pregnancy: Epidemiology, Diagnosis, Management, Surveillance. Curr Obstet Gynecol Rep 11 , 133–141 (2022). https://doi.org/10.1007/s13669-022-00327-6

Download citation

Accepted : 09 February 2022

Published : 19 February 2022

Issue Date : June 2022

DOI : https://doi.org/10.1007/s13669-022-00327-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Molar pregnancy
• Hydatidiform mole
• Complete mole
• Partial mole
• Gestational Trophoblastic Disease
• Surveillance
• Find a journal
• Publish with us
• Track your research

• Open access
• Published: 03 September 2022

Molar pregnancy with a coexisting living fetus: a case series

• Reda Hemida   ORCID: orcid.org/0000-0003-0841-0242 1 ,
• Eman Khashaba 2 &
• Khaled Zalata 3  

BMC Pregnancy and Childbirth volume  22 , Article number:  681 ( 2022 ) Cite this article

4578 Accesses

5 Citations

1 Altmetric

Metrics details

Coexistence of molar pregnancy with living fetus represents a challenge in diagnosis and treatment. The objective of this study to present the outcome of molar pregnancy with a coexisting living fetus who were managed in our University Hospital in the last 5 years.

We performed a retrospective analysis of patients who presented with molar pregnancy with a coexisting living fetus to our Gestational Trophoblastic Clinic, Mansoura University, Egypt from September, 2015 to August, 2020. Clinical characteristics of the patients, maternal complications as well as fetal outcome were recorded. The patients and their living babies were also followed up at least 6 months after delivery.

Twelve pregnancies were analyzed. The mean maternal age was 26.0 (SD 4.1) years and the median parity was 1.0 (range 0–3). Duration of the pregnancies ranged from 14 to 36 weeks. The median serum hCG was 165,210.0 U/L (range 7662–1,200,000). Three fetuses survived outside the uterus (25%), one of them died after 5 months because of congenital malformations. Histologic diagnosis was available for 10 of 12 cases and revealed complete mole associated with a normal placenta in 6 cases (60%) and partial mole in 4 cases (40%). Maternal complications occurred in 6 cases (50%) with the most common was severe vaginal bleeding in 4 cases (33.3%). There was no significant association between B-hCG levels and maternal complications ( P  = 0.3).

Maternal and fetal outcomes of molar pregnancy with a living fetus are poor. Counseling the patients for termination of pregnancy may be required.

Trial registration

The study was approved by Institutional Research Board (IRB), Faculty of Medicine, Mansoura University (number: R.21.10.1492).

Peer Review reports

Introduction

Hydatidiform mole is a rare complication of early pregnancy characterized by disordered proliferation of trophoblastic epithelium and villous edema. It includes complete (CHM) and partial (PHM) hydatidiform moles [ 1 , 2 ]. Partial hydatidiform mole arises as a result of dispermic fertilization of a haploid oocyte, which produces a triploid set of chromosomes and is commonly associated with congenital fetal malformations [ 3 ]. Hydatidiform moles are usually presented with first trimester vaginal bleeding, passage of vesicles, abdominal pain, excessive nausea and vomiting, and rapid abdominal enlargement [ 1 ]. Hyperthyroidism and preeclampsia may be present in some cases of complete hydatidiform moles [ 4 , 5 ]. Human chorionic gonadotropin (hCG) level is elevated but the level in CHM is higher than PHM [ 6 ].

Although complete hydatidiform moles can be easily diagnosed using routine ultrasound assessments early in the first trimester by appearance of snow-storm appearance of the placenta; PHM may mimic missed or incomplete abortion [ 7 ].

During management of molar pregnancy with a coexisting living fetus; the gynecologist should remind that there are three different types. The most common is twin pregnancy with one normal fetus with a normal placenta and a CHM; the second type is twin pregnancy with a normal fetus and placenta and a PHM; and the third, and most uncommon, is a singleton pregnancy consisting of a normal fetus and a placenta with PM changes [ 8 ]. The latter type was reported to occur in 0.005 to 0.01% of all pregnancies [ 9 ]. It is sometimes called “Sad Fetus Syndrome” [ 7 ]. Pregnancy with a PHM and a normal fetus evolves to a viable fetus in less than 25% of cases [ 8 ]. Such pregnancy has little tendency to invade the myometrium and distant metastasis [ 6 ].

Coexistence of molar changes with an apparently healthy fetus is unusual in a case of familial recurrent hydatidiform mole (FRHM). It should be differentiated from mesenchymal dysplasia by morphologic features and immunohistochemistry [ 10 ].

To the best of our knowledge, there are no available international guidelines for management of molar pregnancy with a living fetus. The available publications are mostly case reports, so the authors prepared this manuscript to present the experience of our University GTD referral clinic in the management and outcome of these rare cases.

Patients and methods

In this case series; a retrospective analysis of the patients presented with molar pregnancy with a coexisting living fetus to Gestational Trophoblastic Clinic, Mansoura University, Egypt in 5 years (from September, 2015 to August, 2020). The data of the patients were extracted from the computer and paper files. We included all cases above 18 years with diagnosed molar pregnancy with a living fetus based on clinical, ultrasound, and serum human chorionic gonadotropin (hCG) criteria. The patients who refused to give initial permission to use their data in future research where excluded from the study.

Clinical characteristics including age, parity, obstetric history, gestational age, presenting symptoms, serum hCG on initial diagnosis, and family history, were all recorded. Mode of termination of pregnancy (miscarriage, induction of abortion, hysterotomy, vaginal, or caesarean delivery) was also reported.

Maternal complications during pregnancy, labor, and puerperium were described. Fetal outcomes (miscarriage, congenital fetal malformations, prematurity, or normal) were reported. The patients and living babies were followed up at least for 6 months after delivery .

The study was approved by Institutional Research Board (IRB), Faculty of Medicine, Mansoura University (number: R.21.10.1492). The excel data and figures are anonymous.

Statistical analysis

Data entry and analysis was done using SPSS program, version 23.0 (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp.) was used to analyze the findings. The qualitative data were described in number and percentage. The quantitative data with normal distribution were described in mean and the standard deviation ( \(\pm\) SD). Discrete variables were summarized in median and range. Contingency coefficient Chi square was used to compare nominal variables. The statistical significance was considered when P value was less than 0.05.

From September 2015 to August, 2020; twelve cases of molar pregnancy with living fetus were managed in our hospital. The mean maternal age was 26.0 ( \(\pm\) SD 4.1) years while median parity was 1.0 (range 0–3). Duration of pregnancy ranged from 14 to 36 weeks. The median serum hCG at time of diagnosis was 165,210.0 U/L (range 7662–1,200,000). Ultrasound reports showed well-defined multicystic snowstorm-like mass connecting with placenta (Fig.  1 ). Amniocentesis was performed in one case and revealed a normal diploid female karyotype. During antenatal follow up, the patients who had no complications and requested to undergo conservative treatment were given two injections of 12 mg of betamethasone 24 h apart from 28 weeks of gestation to prevent respiratory distress syndrome.

Ultrasound picture of pregnancy of the case (Z) at 28 weeks showing normal fetus with multiple variable-sized vesicles that cannot be separated from another placenta. The fetus is looking morphologically normal

The fetal outcomes are shown in Table 1 ; as can be noticed that fetuses survived outside the uterus in three cases (25%). The first two cases were delivered by caesarean delivery at 33 and 36 weeks of gestation after development of persistent abdominal pain and dyspnea with marked abdominal enlargement. Polyhydramnios was excluded by ultrasound examination. The third case delivered vaginally at 36 weeks of a neonate with multiple congenital anomalies namely hydrocephalus and macroglossia who died after 5 months. Seven cases continued their pregnancy beyond 20 weeks; five of them delivered prematurely (71.4%). only one case of them survived after neonatal care admission.

For the cases who were subjected to cesarean delivery or hysterectomy; the presence of multiple “grape” vesicles on the maternal surface of the placenta was observed.

Histologic diagnosis was available for 10 of 12 cases and revealed complete mole associated with a normal placenta in 6 cases (60%) and partial mole in 4 cases (40%)( Figs. 2 and 3 ). Immunohistochemistry for P57 gene was performed on two cases (Figs. 2 and 3 ). The first delivered a phenotypically normal alive female baby and its placenta was misdiagnosed as PHM by morphological evaluation but the cytotrophoblast was negative for p57 immunestaining. The second case was diagnosed as dichorionic twins early in pregnancy that was terminated at 14 weeks of gestation because of severe vaginal bleeding. The fetus was phenotypically normal, placenta was histologically normal, and its cytotrophoblast was positive for p57. In addition, there was large amount of molar tissues that was negative for p57 immunostaining demonstrating a diagnosis of a CHM. These data suggest that this conception consists of a dichorionic twins with a living fetus with normal placenta and a CHM (Figs. 2 and 3 ).

Histopathological examination of the coexistent molar tissues of the case (Z): A Complete hydatidiform mole. The picture shows a dilated trophoblastic villous with cistern formation and trophoblastic epithelium hyperplasia (H&E × 100). B Complete hydatidiform mole. The picture shows a negative reaction to p57 IHC (Peroxidase × 100)

Histopathology of the placenta of the second twin of the case (H): A The picture shows normal trophoblastic villi (H&EX100). B P57 immunestaining of the same case shows a diffuse positive reaction in both trophoblastic and stromal cells (Peroxidase × 100)

Maternal complications occurred in 6 cases (50%) with the most common was severe uterine bleeding that was observed in 4 cases (33.3%). Other maternal complications are listed in Table 1 .

Moreover, three of our patients had familial recurrent hydatidiform mole (FRHM).Two of them are sisters. Genetic study through DNA sequencing confirmed NLRP7 mutations that were previously reported [ 11 ]. One of them experienced molar pregnancy with living fetus 3 times when she was aged 25, 27, and 28 years old.

We did not find a significant association between B-hCG level (when considered less than 500,000 and equal or more than 500,000 Unit/liter) and occurrence of maternal complications ( P  = 0.3).

Coexistent molar pregnancy with a living fetus represents a diagnostic and management challenge particularly when the couple is interested to continue pregnancy. In a literature review published by Kawasaki et al. [ 8 ]; eighteen cases of molar pregnancies a coexisting living fetus were reported. The mean gestational age at delivery was 24.5 weeks, and only four fetuses could survive outside the uterus (22.2%) indicating a poor fetal outcome. 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. [ 12 ].

The patients with molar pregnancy with coexistent living fetus who were managed in our university hospital in the last 5 years were presented in this report. Among the 12 reviewed pregnancies; three fetuses survived outside the uterus (25%). However, one of them died after 5 months because of congenital malformations that were reported by other authors [ 3 ]. The overall fetal survival in our series is less than reported in the literature review [ 8 ]. Moreover, Giorgione et al. [ 13 ] reported that overall neonatal survival in their series was 45% (5 of 11); the difference may be related to different patient criteria and neonatal care facilities in different hospitals. Among seven pregnancies continued beyond 20 weeks; five ended in premature deliveries (71.4%), which is much higher than the reported global incidence of prematurity allover pregnancies of 11% [ 14 ].

Amniocentesis is recommended for cases undergoing conservative treatment to exclude chromosomal abnormalities [ 15 ], however, it was performed only in one case in our series. Nine ladies refused the procedure for fear of complications while early pregnancy termination before time of amniocentesis was performed for two patients. In other series [ 13 ], prenatal invasive procedures were performed in 8 of 13 cases (62%). The acceptability of the pregnant ladies to perform prenatal invasive procedures differs from a community to another.

We reported occurrence of maternal complications in 50% of the studied cases; the commonest was severe vaginal bleeding. Although Sánchez-Ferrer et al. [ 15 ] concluded that termination of pregnancy is not indicated if the fetus is normal and continuation to birth is possible in nearly 60% of cases with no increase in maternal risks when the patient is closely monitored after birth until B-hCG is negative. The difference may be due to different number of cases in each study.

Moreover, two of the managed cases (16.7%) were complicated with early-onset preeclampsia and subsequently the pregnancy was terminated at 22 and 14 weeks of gestation. This finding was also reported by Kawasaki et al. [ 8 ]. In our series, we observed one case of complete mole that progressed to GTN (8.3%) and was successfully treated with single-agent chemotherapy, which is similar to a previous case scenario reported by Peng et al. [ 16 ].

The diagnostic challenge of a case of molar pregnancy with a coexisting living fetus 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 [ 17 ]. Shaaban et al. [ 18 ] suggested that the peculiar “twin peak” sign in ultrasound, 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, confirming the presence of a dichorionic twin gestation.

P57 immunestaining was performed in 2 cases of molar pregnancy with apparently normal fetus (Figs. 2 and 3 ) that confirmed these cases had a dichorionic twin pregnancy consisting of a complete mole with a co-twin of normal fetus and placenta. However, these cases may have been misdiagnosed as partial mole especially when the first ultrasound was done late in pregnancy. Other authors also reported cases of term deliveries of a complete hydatidiform mole with a coexisting living fetus [ 16 , 19 , 20 ].

We did not find a significant association between B-hCG level (when considered less than 500,000 and equal or more than 500,000 Unit/liter) and occurrence of maternal complications ( P  = 0.3). This finding was in agree with Chale-Matsau et al. [ 21 ] who concluded that the β-hCG levels do not always correlate with disease severity and prognosis in patients with GTD.

With respect to the reported maternal and fetal complications in our study and other reports, it is necessary to fully inform the pregnant woman of the possible maternal and fetal complications, such as preeclampsia, hyperthyroidism, vaginal bleeding, and theca lutein ovarian cysts. The probability of postpartum development into persistent trophoblastic disease is also high.

The limitations of this study are its retrospective design, limited number of cases, and availability immunohistochemical study of only two cases.

Maternal and fetal outcome of molar pregnancy with a living fetus is poor. The incidence of prematurity is high (71.4%). Counseling of the patients for termination of pregnancy may be need. A global guideline for management is required.

Availability of data and materials

Original data and materials are available on request after contacting the corresponding author.

Abbreviations

Gestational trophoblastic neoplasia

Complete hydatidiform mole

Partial hydatidiform mole

B subunit of human chorionic gonadotropin

Standard deviation

Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol. 2010;203(6):531–9.

Article   Google Scholar  

Seckl M, Sebire N, Fisher R, Golfier F, Massuger L, Sessa C, et al. Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(suppl_6):vi39–50.

Stevens FT, Katzorke N, Tempfer C, Kreimer U, Bizjak GI, Fleisch MC, Fehm TN. Gestational Trophoblastic Disorders: An Update in 2015. Geburtshilfe Frauenheilkd. 2015;75(10):1043–50.

Article   CAS   Google Scholar  

Walkington L, Webster J, Hancock BW, Everard J, Coleman RE. Hyperthyroidism and human chorionic gonadotrophin production in gestational trophoblastic disease. Br J Cancer. 2011;104(11):1665–9.

Iriyama T, Wang G, Yoshikawa M, et al. Increased LIGHT leading to sFlt-1 elevation underlies the pathogenic link between hydatidiform mole and preeclampsia. Sci Rep. 2019;9(1):10107.

Soper JT. Gestational Trophoblastic Disease: Current Evaluation and Management. Obstet Gynecol. 2021;137(2):355–70.

Rathod AD, Pajai SP, Gaddikeri A. Partial mole with a coexistent viable fetus—a clinical dilemma: a case report with review of literature. J South Asian Feder Obstet Gynaecol. 2014;6:51–5.

Kawasaki K, Kondoh E, Minamiguchi S, Matsuda F, Higasa K, Fujita K, Mogami H, Chigusa Y, Konishi I. Live-born diploid fetus complicated with partial molar pregnancy presenting with pre-eclampsia, maternal anemia, and seemingly huge placenta: A rare case of confined placental mosaicism and literature review. J Obstet Gynaecol Res. 2016;42(8):911–7.

Smith HO, Kohorn E, Cole LA. Choriocarcinoma and gestational trophoblastic disease. Obstet Gynecol Clin North Am. 2005;32(4):661–84.

Sebire NJ, Fisher RA. Partly molar pregnancies that are not partial moles: additional possibilities and implications. Pediatr Dev Pathol. 2005;8(6):732–3.

Rezaei M, Suresh B, Bereke E, Hadipour Z, Aguinaga M, Qian JH, Bagga R, Fardaei M, Hemida R, Jagadeesh S, Majewski J, Slim R. Novel pathogenic variants in NLRP7, NLRP5 and PADI6 in patients with recurrent hydatidiform moles and reproductive failure. Clin Genet. 2021;99(6):823–8.

Højberg KE, Aagaard J, Henriques U, Sunde L. Placental vascular malformation with mesenchymal hyperplasia and a localized chorioangioma. A rarity simulating partial mole. Pathol Res Pract. 1994;190(8):808–13. https://doi.org/10.1016/S0344-0338(11)80429-2 (discussion 814).

Article   PubMed   Google Scholar  

Giorgione V, Cavoretto P, Cormio G, Valsecchi L, Vimercati A, De Gennaro A, Rabaiotti E, Candiani M, Mangili G. Prenatal Diagnosis of Twin Pregnancies with Complete Hydatidiform Mole and Coexistent Normal Fetus: A Series of 13 Cases. Gynecol Obstet Invest. 2017;82(4):404–9.

Walani SR. Global burden of preterm birth. Int J Gynaecol Obstet. 2020;150(1):31–3.

Sánchez-Ferrer ML, Ferri B, Almansa MT, Carbonel P, López-Expósito I, Minguela A, Abad L, Parrilla JJ. Partial mole with a diploid fetus: case study and literature review. Fetal Diagn Ther. 2009;25(3):354–8.

Peng HH, Huang KG, Chueh HY, Adlan AS, Chang SD, Lee CL. Term delivery of a complete hydatidiform mole with a coexisting living fetus followed by successful treatment of maternal metastatic gestational trophoblastic disease. Taiwan J Obstet Gynecol. 2014;53(3):397–400.

Kutuk MS, Ozgun MT, Dolanbay M, Batukan C, Uludag S, Basbug M. Sonographic findings and perinatal outcome of multiple pregnancies associating a complete hydatiform mole and a live fetus: a case series. J Clin Ultrasound. 2014;42(8):465–71.

Shaaban AM, Rezvani M, Haroun RR, et al. Gestational Trophoblastic Disease: Clinical and Imaging Features. Radiographics. 2017;37(2):681–700.

Sasaki Y, Ogawa K, Takahashi J, Okai T. Complete hydatidiform mole coexisting with a normal fetus delivered at 33 weeks of gestation and involving maternal lung metastasis: a case report. J Reprod Med. 2012;57(7–8):301–4 (PMID: 22838245).

PubMed   Google Scholar  

Malhotra N, Deka D, Takkar D, Kochar S, Goel S, Sharma MC. Hydatidiform mole with coexisting live foetus in dichorionic twin gestation. Eur J Obstet Gynecol Reprod Biol. 2001;94:301–3.

Chale-Matsau B, Mokoena S, Kemp T, Pillay TS. Hyperthyroidism in molar pregnancy: β-HCG levels do not always reflect severity. Clin Chim Acta. 2020;511:24–7.

Download references

Acknowledgements

Not applicable.

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). No funding was received.

Author information

Authors and affiliations.

Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Mansoura University, 35111 Elgomhuria street, Mansoura, Egypt

Reda Hemida

Department of Community Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Eman Khashaba

Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Khaled Zalata

You can also search for this author in PubMed   Google Scholar

Contributions

R.H: Conception of Idea, collection of data, and editing manuscript. E.K: Statistical analysis and editing manuscript. K.Z: Pathology revision, preparation of figures, and revision of manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Reda Hemida .

Ethics declarations

Ethics approval and consent to participate.

The study was approved by Institutional Research Board (IRB), Faculty of Medicine, Mansoura University (number: R.21.10.1492). An informed consent for participation in the study was obtained from all participants.

All experiments were performed in accordance with relevant guidelines and regulations.

Consent for publication

An informed consent for publication in an online open-access journal was obtained from the study participants.

Competing interests

No competing interests that are directly or indirectly related to the work submitted for publication.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Hemida, R., Khashaba, E. & Zalata, K. Molar pregnancy with a coexisting living fetus: a case series. BMC Pregnancy Childbirth 22 , 681 (2022). https://doi.org/10.1186/s12884-022-05004-3

Download citation

Received : 14 February 2022

Accepted : 26 August 2022

Published : 03 September 2022

DOI : https://doi.org/10.1186/s12884-022-05004-3

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Molar pregnancy
• Living fetus

BMC Pregnancy and Childbirth

ISSN: 1471-2393

• Submission enquiries: [email protected]
• General enquiries: [email protected]

• Patient Care & Health Information
• Diseases & Conditions
• Molar pregnancy

A molar pregnancy is a rare complication of pregnancy. It involves unusual growth of cells called trophoblasts. These cells typically become the organ that feeds a growing fetus. That organ also is known as the placenta.

There are two types of molar pregnancy — complete molar pregnancy and partial molar pregnancy. In a complete molar pregnancy, the placental tissue swells and appears to form fluid-filled cysts. There is no fetus.

In a partial molar pregnancy, the placenta might have both regular and irregular tissue. There may be a fetus, but the fetus can't survive. The fetus usually is miscarried early in the pregnancy.

A molar pregnancy can have serious complications, including a rare form of cancer. A molar pregnancy requires early treatment.

During a molar pregnancy, the placenta doesn't form typically. It can look like a mass of cysts. The fetus either doesn't form or doesn't form regularly and can't survive.

A molar pregnancy may seem like a regular pregnancy at first. But most molar pregnancies cause symptoms that can include:

• Dark brown to bright red bleeding from the vagina during the first three months
• Severe nausea and vomiting
• Sometimes grapelike cysts that pass from the vagina
• Pelvic pressure or pain

Because of improved ways of detecting a molar pregnancy, most are found in the first trimester. If it is not found in the first three months, symptoms of a molar pregnancy might include:

• A uterus growing quickly and being too large early in the pregnancy
• Preeclampsia — a condition that causes high blood pressure and protein in the urine — before 20 weeks of pregnancy
• Ovarian cysts
• Overactive thyroid, also known as hyperthyroidism

An egg fertilized atypically causes a molar pregnancy. Human cells usually have 23 pairs of chromosomes. In a typical fertilization, one chromosome in each pair comes from the father, the other from the mother.

In a complete molar pregnancy, one or two sperm fertilize an egg. The chromosomes from the mother's egg are missing or don't work. The father's chromosomes are copied. There's none from the mother.

In a partial or incomplete molar pregnancy, the mother's chromosomes are present, but the father supplies two sets of chromosomes. The embryo then has 69 chromosomes instead of 46. This most often occurs when two sperm fertilize an egg, resulting in an extra copy of the father's genes.

Risk factors

Factors that can contribute to a molar pregnancy include:

• Earlier molar pregnancy. If you've had one molar pregnancy, you're more likely to have another. A repeat molar pregnancy happens, on average, in 1 out of every 100 people.
• Age of the mother. A molar pregnancy is more likely in people older than age 43 or younger than age 15.

Complications

After removing a molar pregnancy, molar tissue might remain and continue to grow. This is called persistent gestational trophoblastic neoplasia (GTN). GTN happens more often in complete molar pregnancies than it does in partial molar pregnancies.

One sign of persistent GTN is a high level of human chorionic gonadotropin (HCG) — a pregnancy hormone — after the molar pregnancy has been removed. In some cases, the mole that causes the molar pregnancy goes deep into the middle layer of the uterine wall. This causes bleeding from the vagina.

Persistent GTN is usually treated with chemotherapy. Another treatment possibility is removal of the uterus, also known as hysterectomy.

Rarely, a cancerous form of GTN known as choriocarcinoma develops and spreads to other organs. Choriocarcinoma is usually successfully treated with chemotherapy. A complete molar pregnancy is more likely to have this complication than is a partial molar pregnancy.

If you've had a molar pregnancy, talk to your pregnancy care provider before trying to get pregnant again. You might want to wait six months to one year. The risk of having another molar pregnancy is low, but it's higher once you've had a molar pregnancy.

During future pregnancies, a care provider may do early ultrasounds to check your condition and make sure the baby is developing.

• Ferri FF. Molar pregnancy. In: Ferri's Clinical Advisor 2023. Elsevier; 2023. https://www.clinicalkey.com. Accessed Oct. 3, 2022.
• Berkowitz RS, et al. Hydatidiform mole: Epidemiology, clinical features, and diagnosis. https://www.uptodate.com/contents/search. Accessed Oct. 3, 2022.
• Walls RM, et al., eds. Complications of pregnancy. In: Rosen's Emergency Medicine Concepts and Clinical Practice. 10th ed. Elsevier; 2023. https://www.clinicalkey.com. Accessed Oct. 3, 2022.
• About gestational trophoblastic disease. American Cancer Society. https://www.cancer.org/cancer/gestational-trophoblastic-disease.html. Accessed Oct. 3, 2022.
• Berkowitz RS, et al. Hydatidiform mole: Treatment and follow-up. https://www.uptodate.com/contents/search. Accessed Oct. 3, 2022.
• Ning F, et al. Understanding and management of gestational trophoblastic disease . F1000 Faculty Review. 2019; doi:10.12688/f1000research.14953.1. Accessed Oct. 3, 2022.
• Frequently asked questions. Dilation and curettage FAQ062. American College of Obstetricians and Gynecologists. https://www.acog.org/womens-health/faqs/dilation-and-curettage. Accessed Oct. 3, 2022.
• Horowitz NS, et al. Epidemiology, diagnosis and treatment of gestational trophoblastic disease: A Society of Gynecologic Oncology evidence-based review and recommendation. Gynecologic Oncology; 2021. doi:10.1016/j.ygyno.2021.10.003.

Associated Procedures

• Dilation and curettage (D&C)
• Symptoms & causes
• Diagnosis & treatment

Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission.

• Opportunities

Mayo Clinic Press

Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press .

• Mayo Clinic on Incontinence - Mayo Clinic Press Mayo Clinic on Incontinence
• The Essential Diabetes Book - Mayo Clinic Press The Essential Diabetes Book
• Mayo Clinic on Hearing and Balance - Mayo Clinic Press Mayo Clinic on Hearing and Balance
• FREE Mayo Clinic Diet Assessment - Mayo Clinic Press FREE Mayo Clinic Diet Assessment
• Mayo Clinic Health Letter - FREE book - Mayo Clinic Press Mayo Clinic Health Letter - FREE book

Your gift holds great power – donate today!

Make your tax-deductible gift and be a part of the cutting-edge research and care that's changing medicine.

Atypical presentation of molar pregnancy

Affiliation.

• 1 Department of Obstetrics and Gynaecology, Our Lady of Lourdes Hospital, Drogheda, Ireland.
• PMID: 30262528
• PMCID: PMC6169626
• DOI: 10.1136/bcr-2018-225545

The classic features of molar pregnancy are irregular vaginal bleeding, hyperemesis, enlarged uterus for gestational age and early failed pregnancy. Less common presentations include hyperthyroidism, early onset pre-eclampsia or abdominal distension due to theca lutein cysts. Here, we present a case of molar pregnancy where a woman presented to the emergency department with symptoms of acute abdomen and was treated as ruptured ectopic pregnancy. The woman underwent laparoscopy and evacuation of retained products of conception. Histological examination of uterine curettage confirmed the diagnosis of a complete hydatidiform mole. The woman was discharged home in good general condition with a plan for serial beta-human chorionic gonadotropin (beta-hCG) follow-up. Complete follow-up includes use of contraception and follow-up after beta-hCG is negative for a year.

Keywords: obstetrics and gynaecology; pregnancy; reproductive medicine.

© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.

Publication types

• Case Reports
• Abdominal Pain / etiology
• Blood Transfusion
• Cholangiopancreatography, Endoscopic Retrograde
• Chorionic Gonadotropin, beta Subunit, Human / blood
• Hydatidiform Mole / complications
• Hydatidiform Mole / diagnosis*
• Hydatidiform Mole / therapy
• Laparoscopy
• Ultrasonography
• Uterine Hemorrhage / etiology
• Uterine Neoplasms / complications
• Uterine Neoplasms / diagnosis*
• Uterine Neoplasms / therapy
• Chorionic Gonadotropin, beta Subunit, Human

Log in using your username and password

• Search More Search for this keyword Advanced search
• Latest content
• Global health
• BMJ Journals More You are viewing from: Google Indexer

You are here

• Volume 14, Issue 7
• Thyrotoxicosis: a rare presentation of molar pregnancy
• Article Text
• Article info
• Citation Tools
• Rapid Responses
• Article metrics

• http://orcid.org/0000-0001-8549-1969 Eison De Guzman 1 ,
• Hira Shakeel 2 and
• Rohit Jain 2
• 1 Department of Internal Medicine , The George Washington University Hospital , Washington , District of Columbia , USA
• 2 Department of Endocrinology and Metabolism , The George Washington University Hospital , Washington , District of Columbia , USA
• Correspondence to Dr Eison De Guzman; icydeg1{at}gmail.com

A 49-year-old woman, G8P7, presented with 1 week of worsening vaginal bleeding and abdominal cramps in the setting of a recently discovered unplanned pregnancy. Vaginal ultrasound findings and a significantly elevated human chorionic gonadotropin (hCG) level were concerning for molar pregnancy. She developed signs of hyperthyroidism on the night of admission, for which the endocrinology team was consulted. Laboratory data were consistent with hyperthyroidism. The patient was believed to have thyrotoxicosis secondary to molar pregnancy with concern for impending thyroid storm. Her mental health disorder and bacteraemia made taking care of her further challenging. She was started on a beta-blocker, antithyroid agent and intravenous corticosteroids. She underwent an uncomplicated suction dilation and curettage (D&C), with resolution of her symptoms a few days after. At a follow-up appointment, the patient continued to be asymptomatic and was feeling well.

• thyroid disease
• thyrotoxicosis

https://doi.org/10.1136/bcr-2021-242131

Statistics from Altmetric.com

Request permissions.

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Molar pregnancy is a relatively rare complication of gestation with an incidence reported in the USA to be 121 per 100 000 pregnancies. 1 This complication occurs when there is an abnormal proliferation of trophoblastic tissue, resulting in a non-viable mass that often resembles grape-like structures. The major risk factors for molar pregnancy are prior gestational trophoblastic disease and increased maternal age, especially greater than age 45. 1

The most common presenting symptom of molar pregnancy is vaginal bleeding. Hyperemesis gravidarum is a classic association, but presents less frequently than vaginal bleeding. 2 An even rarer complication of molar pregnancy is thyrotoxicosis. Although increased thyroid function is often reported in gestational trophoblastic disease, only 5% of these cases show symptoms of hyperthyroidism. It is believed that an elevated hCG level >200 000 IU/L for several weeks is necessary for the development of thyrotoxicosis. 3 Treatment is necessary to alleviate the patient’s symptoms and to prevent progression into thyroid storm. Thyroid storm is a lethal condition that, even when treated, has a mortality rate as high as 50%. 4

We report a case of molar pregnancy in which the patient subsequently developed thyrotoxicosis. This case highlights the rare complications of molar pregnancy, and the importance of monitoring for clinical hyperthyroidism in this patient population. The case demonstrates how effective treatment of thyrotoxicosis in molar pregnancy not only alleviates the patient’s symptoms, but also helps to prevent progression into the highly lethal thyroid storm.

Case presentation

A 49-year-old woman, G8P7, with asthma and bipolar disorder presented to her primary care provider with nausea, vomiting and bilateral breast tenderness. At the visit, a qualitative urine pregnancy test was positive, revealing an unplanned pregnancy. The patient then began to experience intermittent vaginal spotting that eventually increased to soaking multiple pads throughout the day. This was associated with abdominal cramps that prompted her visit to the emergency room. She had seven uncomplicated vaginal deliveries in the past, the most recent of which was 10 years ago. She has no personal or family history of fibroids, cervical cancer or molar pregnancy.

On admission, the patient was haemodynamically stable with generalised abdominal tenderness on examination. According to her last menstrual period, the estimated gestational age was 15 weeks. She was admitted to the obstetrics and gynecology (OBGYN) team. Later that night, she developed a fever of 39.4°C associated with sinus tachycardia, diaphoresis and tremors in her extremities. On day 2 of admission, she was found to have laboratory data consistent with hyperthyroidism at which point the endocrinology team was consulted.

Investigations

Prior to the endocrinology consultation, the patient underwent a vaginal ultrasound that revealed an enlarged and irregular cystic-appearing endometrium without an intrauterine gestational sac ( figures 1 and 2 ). β-hCG level was disproportionately elevated to 414 600 IU/L given the gestational age. These findings were concerning for molar pregnancy. Her thyroid studies showed an undetectable Thyroid-stimulating hormone (TSH) (<0.015 μIU/mL; first trimester reference range 0.60–3.40), elevated free T4 (3.73 ng/dL; first trimester reference range 0.8–1.2) and elevated free T3 (10.0 pg/mL; first trimester reference range 4.1–4.4). Blood cultures from the day she spiked a fever eventually grew Salmonella species. CT chest/abdomen/pelvis did not reveal a source of the infection, nor did it show evidence of metastases.

• Download figure
• Open in new tab
• Download powerpoint

Transvaginal ultrasound showing lack of intrauterine sac and abnormal placental tissue with fluid-filled cysts in longitudinal view.

Transvaginal ultrasound showing lack of intrauterine sac and abnormal placental tissue with fluid-filled cysts in transverse view.

Differential diagnosis

The patient’s presentation and workup were consistent with molar pregnancy (nausea, vomiting, vaginal bleeding, ultrasound with no intrauterine sac but with cystic appearance, and significantly elevated hCG). Her laboratory studies showed a new hyperthyroid state (compared with baseline normal Thyroid function tests (TFTs) obtained a few years ago during psychiatric evaluation), and she experienced symptoms of tachycardia, heat intolerance, diaphoresis and tremors. Therefore, the leading differential was thyrotoxicosis secondary to molar pregnancy, as stimulation of TSH receptors by the beta subunit of hCG can cause increased production and release of thyroid hormones. 5

Other causes of hyperthyroidism were also considered but deemed less likely clinically. The patient lacked a goitre, pretibial myxoedema, exophthalmos or lid lag to suggest Graves’ disease, although TSH receptor and thyroid peroxidase antibodies were not collected during the admission. She has no history of any thyroid disorders in the family. There was no preceding viral upper respiratory tract infection or neck tenderness to indicate subacute thyroiditis. Fibrinogen was mildly elevated to 558 mg/dL in the setting of concurrent salmonella bacteraemia. In painless (silent) thyroiditis, T4 is usually disproportionately elevated compared with T3, which was the opposite in this case. 6 The patient’s home medications were reviewed, and no medications were found that are classically linked to thyroiditis. She does have a history of bipolar disorder, but it has been managed with olanzapine and fluoxetine without prior lithium use. There was no recent iodinated contrast media exposure prior to the development of her symptoms. A thyroid ultrasound was not obtained prior to her emergent intervention.

Infection, such as endometritis, was also on the differential before the blood cultures turned positive, given the fever and tachycardia. Although bacteraemia could explain these abnormal vital signs, it does not account for her other symptoms of heat intolerance and tremors. Besides an enlarged endometrium, the vaginal ultrasound did not show signs of endometritis. The patient also lacked productive cough or dysuria to suggest other infectious aetiologies.

Lastly, the patient had multiple admissions in the past with tachycardia that spontaneously resolved. Her tachycardia then was attributed to excessive caffeine consumption (drinking 4–6 cups of coffee in the morning), as well as frequent use of her albuterol inhaler. However, the patient currently only drinks one cup of coffee a day and has not used her albuterol inhaler in over 2 weeks. She also did not have significant anaemia or decreased urine output to suggest hypovolaemia as a cause of the tachycardia.

After reviewing the patient’s case, the endocrinology team reached a consensus that the patient was suffering from thyrotoxicosis secondary to her molar pregnancy. The patient was scheduled for a suction dilation and curettage to evacuate the mole and remove the ultimate source of the β-hCG. On day 2 of admission, she was started on propranolol (not administered due to hypotension) and propylthiouracil (PTU) (500 mg loading dose, followed by 100 mg every 8 hours) to decrease sympathetic hyperactivity and thyroid hormone production, respectively. Although methimazole has a more rapid onset and better side effect profile than PTU, this patient also had significantly elevated free T3 levels, so PTU was chosen for its ability to prevent T4 to T3 conversion. 7 After discussion with the OBGYN team, there was initially low suspicion for infection (before blood cultures resulted), so the patient was also started on intravenous hydrocortisone (300 mg loading dose, followed by 100 mg every 8 hours). The decision to start steroids was based on concern of thyroid storm occurring in the perioperative period. At the time the endocrinology team was consulted, the patient had a Burch-Wartofsky Point Scale score of 40, which suggests impending thyroid storm. 4 Furthermore, steroids also help decrease conversion of T4 to the more active T3 hormone. 8

Overnight, the patient became hypotensive and persistently tachycardic. Due to concerns of sepsis, the OBGYN team performed an emergent suction D&C early on day 3 of admission. Specimen was collecting during the procedure, and pathology revealed diploidy with negative p57 immunohistochemistry stain, consistent with a complete hydatidiform mole.

Outcome and follow-up

After suction D&C, the patient was closely monitored for thyroid storm in the postoperative period, with no worsening of her symptoms. Four days after the procedure, her tachycardia, tremors, diaphoresis and heat intolerance finally resolved. Her thyroid function tests also improved (FT3 3.0 pg/mL, FT4 1.52 ng/dL, TSH 0.016 μIU/mL) ( table 1 ). Her β-hCG level decreased to 14 744 from 414 600 IU/L. Propranolol and PTU were discontinued at that time since the patient was no longer symptomatic. The intravenous steroids were discontinued soon after the procedure due to the patient’s blood cultures turning positive and eventually growing Salmonella species. A CT chest/abdomen/pelvis performed to identify an infectious source was unrevealing. Per discussion with the infectious disease team, the Salmonella bacteraemia was likely secondary to bacterial translocation from the gastrointestinal tract, and the patient was discharged with ciprofloxacin (500 mg two times per day) to complete a 2-week course of antibiotics. She was counselled on molar pregnancy and complications of pregnancy at an advanced maternal age. The importance of contraception use during this postoperative period was emphasised, in order to monitor for a rise in β-hCG that may indicate development of gestational trophoblastic neoplasia (GTN). Imaging is useful not only in diagnosing hydatidiform moles, but also in detecting complications such as GTN metastases, the most common site being the lung. 9 In our patient, a chest x-ray and CT chest/abdomen/pelvis did not show any evidence of metastatic disease. Labwork performed 2 weeks after discharge showed continued improvement of her TFTs and β-hCG levels.

• View inline

TFTs and β-hCG (Beta human chorionic gonadotropin) levels

Molar pregnancy is part of a spectrum of diseases known as gestational trophoblastic diseases. It is a complication defined by abnormal benign or malignant proliferation of trophoblastic cells which result in markedly elevated β-hCG levels. Gestational trophoblastic disease can cause secondary hyperthyroidism as a result of structural homology between β-hCG and TSH. Hormones such as TSH, Follicle-stimulating hormone (FSH), Luteinizing hormone (LH) and hCG are heterodimeric glycoprotein hormones that have an alpha subunit and a beta subunit. The alpha subunit is common to all these hormones. Moreover, there is structural similarity between hCG and TSH beta subunits. Laboratory studies have revealed that normal β-hCG has weak thyrotropic activity on thyroid TSH receptors. 10 One unit of β-hCG has the reactivity equivalent to 0.0013 uU of TSH. The level of sialylation of β-hCG determines its bioreactivity on the TSH receptors: the higher the degree of sialylation, the less activity β-hCG will have. The β-hCG produced by hydatidiform moles has greater thyrotropic activity than normal β-hCG due to its decreased sialylation. 11 Moreover, the extent of desialylation of β-hCG varies with each molar pregnancy. One unit of β-hCG produced by Gestational trophoblastic disease (GTD) has thyrotropic activity range from 3.72 to 46.8 uU equivalents of TSH. 12 It is estimated that for every 10 000 IU/L increase in hCG, there is a 0.1 μIU/mL decrease in TSH and 0.1 ng/dL increase in free T4. 13

Increased levels of β-hCG concentration cause a weak hyperthyroid state in a normal pregnancy. The degree of hyperthyroidism is exacerbated by molar pregnancy with elevated levels of β-hCG and decreased levels of sialylation. The extent and development of hyperthyroidism, thyrotoxicosis, and ultimately thyroid storm is determined by multiple factors: the levels of β-hCG, the amount of desialylation, as well as the duration and type of molar pregnancy.

Compared with partial hydatidiform moles, complete hydatidiform moles usually have higher β-hCG levels. 14 Therefore, it is not surprising that complete moles have been associated with more severe hyperthyroidism. In one Turkish study, patients with complete moles were found to have significantly lower TSH levels and higher free T4 levels compared with those with partial moles. 15 The patients diagnosed with complete moles were also significantly older and of higher gravidity than the patients diagnosed with partial moles. Our patient, who was diagnosed with a complete mole, was 49 years old with seven prior pregnancies. A recent case report describing thyroid storm in a complete molar pregnancy also consisted of an older maternal age woman with multiple pregnancies (G7P3033). 16

In the past few decades, physicians have diagnosed molar pregnancies at earlier gestational ages. One Brazilian study found that the average gestational age at time of diagnosis from 1988 to 1992 was 15 weeks, compared with only 10 weeks in 2008–2012. 17 This earlier detection is promoted by the increased utilisation of first trimester ultrasound and β-hCG levels for screening of prenatal conditions. 18 In our patient, the later diagnosis at 15 weeks gestation was likely due to a delay in seeking medical care after having missed her period.

Treatment of thyrotoxicosis or thyroid storm is based on managing the four major elements involved: the precipitating event; the thyroid gland; the peripheral effects of thyroid hormone and systemic decompensation, if any. The precipitating event in our case was molar pregnancy with the definitive treatment being evacuation. Thyroid hormone synthesis can be curbed with PTU or methimazole, and hormone release can be decrease with iodine. PTU and glucocorticoids can dampen the peripheral effects of thyroid hormone by decreasing the rate of conversion of T4 to the more active T3. Beta blockers, specifically propranolol and esmolol, can decrease the peripheral effects of thyroid hormone by blocking the receptors on which T3 acts. In severe illness, plasmapheresis and charcoal plasma perfusion can help remove excess hormone. 19

In our patient, due to active infection, steroids were discontinued after two doses and propranolol was not administered given low blood pressure. She essentially received 5 days of PTU therapy, which was discontinued once her FT4 normalised before discharge. Given that she had suction dilatation and curettage done in an appropriate and timely manner, her thyroid function tests continued to improve following the procedure as did her clinical status.

Patient’s perspective

When I found out I was pregnant, I had no idea about a molar pregnancy. When I realised there was no baby, I was confused. I’ve never had a miscarriage. All my children were live births, so this was strange. I knew something was wrong when I started vomiting so much. I felt like it was killing me. I believe that if I hadn’t come to the doctor, I would have laid in bed and died. I knew I had to come see somebody to find out what was going on with me. I was too sick for a normal pregnancy or even a miscarriage. It took me a while to accept that there was no baby. I was a little sad because I felt like I’ve been punished. Im being honest, I don’t wish this type of pain and illness on anybody. Constantly throwing up, the stomach pain, I don’t want anyone to have to go through this. I want people to know about this disease, so they can avoid what I’ve been through. I am thankful that the surgery went well. I feel that my health is better now. I hope I never experience this again, and that nobody else has to experience it. It’s worse than actually having a baby.

Learning points

In patients with molar pregnancies, it is essential to monitor for rare complications such as thyrotoxicosis.

Treatment of thyrotoxicosis in molar pregnancies, especially those with significantly elevated β-hCG levels and undetectable TSH levels, is important to prevent progression to thyroid storm.

Counselling patients about the risks associated with advanced maternal age pregnancy is necessary for the health of both fetus and mother, and can prevent undesired complications, such as molar pregnancy and thyrotoxicosis in this case.

Ethics statements

Patient consent for publication.

• Altieri A ,
• Franceschi S ,
• Ferlay J , et al
• Soto-Wright V ,
• Bernstein M ,
• Goldstein DP , et al
• Hershman JM
• Wartofsky L
• Nisula BC ,
• Taliadouros GS
• Williams DE ,
• Chopra IJ ,
• Orgiazzi J , et al
• Polizio R ,
• Fushida K , et al
• Yoshimura M ,
• Pekary AE ,
• Pang XP , et al
• Yamazaki K ,
• Shizume K , et al
• Lockwood CM ,
• Grenache DG ,
• Gronowski AM
• Schink JC , et al
• Düğeroğlu H ,
• Özgenoğlu M
• Schreyer KE
• Maestá I , et al
• Pereira JV-B ,
• Moskovitz JB ,

Contributors EDG, HS and RJ were directly involved in the patient’s care. EDG and HS drafted the manuscript under the supervision of RJ, who provided guidance for the final manuscript. All authors contributed to the final version of the manuscript.

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.

Provenance and peer review Not commissioned; externally peer reviewed.

Read the full text or download the PDF:

Follow us on :

Take a look at the Recent articles

Molar pregnancy-case report, marina yuabova.

La Guardia Community College, City University of New York, NY, USA

E-mail : aa

DOI: 10.15761/CCRR.1000430

Molar pregnancy is formed as a result of divergent fertilization process that leads to production of atypical tissue within the uterus. It categorized in two groups: partial and complete.

Complete mole involves absence of the embryo, where partial mole demonstrates presence of fetal parts.  Molar pregnancy does not result in viable fetus, early detection and treatment is essential for positive outcome.

Patient has presented with typical signs and symptoms for molar pregnancy including vaginal spotting with dark brown grape like substance, law hemoglobin, fundal height greater then expected (as for gestational age), nausea and vomiting.

Writer will present case of molar pregnancy, risk factors, typical presentation and treatment modality.

moles, hydatidiform moles, molar pregnancy

Introduction

Hydatidiform mole is a product of anomalous conceptions, with prevalence about 1 in 500-1000 pregnancies [6]. All cases could be categorized in to two groups, complete or partial hydatidiform mole.  In complete molar pregnancy diffuse swelling of chorionic villi and disseminated thromboplastic hyperplasia without embryo or fetal tissues is characteristic. These cases commonly have a diploid karyotype [4]. In opposite, partial molar pregnancy displays central swelling of the chorionic villi and thromboplastic hyperplasia. Some parts of fetal and embryonic tissues are commonly present [7]. All molar pregnancies included defective ovum flawed maternal chromosomal deoxyribonucleic acid, suggesting only of hydatidiform mole has been identified, one of which is advanced maternal age and history of previous molar pregnancies [7]. Despite the fact there are some evidence accessible in regards to definitive risk of consecutive hydatidiform moles after previous partial or complete moles [3,5]. In cases where fetuses with partial moles are pinpointed, they consistently bear association with congenital anomalies, such as cleft lip and syndactyly [5].

Case Report

A 19-year-old female patient reported to OB-GYN clinic for annual examination during the initial interview she complained of very unusual menstrual bleeding, which began 3 days ago, patient has also reported abdominal cramping, nausea, vomiting and lower back pain. Patient admitted to be sexually active but was using calendar method as birth control. Her last menstrual period was exactly 5 weeks ago.  Patients past medical and family history are unremarkable. She denied to have any allergies, denied drinking alcoholic beverages but admitted to be an active smoker; she currently smokes 0.5 packs of cigarettes per day. The patient was alert, oriented and in obvious distress.  Her temperature was 98.6 F, blood pressure 119/64 mmHg, heart rate 123 bpm, respiratory rate of 16 breaths per min with a pulse oximetry of 98% on room air. On physical exam her skin was cool and clammy and patient's breathing was mildly labored, with thread peripheral pulses. Her fundal height was 2 cm below umbilicus. Abdomen was soft and mildly tender on lower quadrants bilaterally. Her lower extremities were WNL. During Pelvic examination reported loose discharge of blood, clots and a large amount of brown-colored grapelike material. The cervical OS was dilated to approximately 2cm with some cervical motion tenderness. After patient has been transferred to ER blood was collected and sent to lab for analysis, laboratory results as follows: hemoglobin of 8.6 g/dL, hematocrit of 7.5%, white blood count at 16,000 with 78% neutrophils and 5% bands, platelets at 123,000, international normalized ratio of 1.5, and bicarbonate of 14 mmol/L. Bun was elevated at 38 mg/dL and creatinine was 0.7 mg/dL.  Beta HCG was 360,514 mIU/mL. IV line was initiated; patient has received 1000 cc bolus of 0.9% of sodium chloride, which followed with infusion rate at 125 cc per hour. Case has been discussed with OB consult and Pelvic Sonogram was performed. Pelvic- sonogram reviled a cloud like image, with absence for heartbeat. Patient was transferred to OR rapidly and two units of crossed matched blood were infused.  Dilatation and curettage was performed in OR.

Surgical pathology confirmed a complete hydatidiform mole. Patient’s recovery was unremarkable; patient was discharged home after 48 hours. The patient was instructed on importance of using reliable method of birth control and monitoring of levels of HCG (first 48 hours post evacuation, weekly until hcg <5 miu/ml, then monthly X 6-12 months).

Molar pregnancies are classified as nonviable conceptions and are medically termed hydatidiform moles [3]. They are masses of cysts or benign tumors with a grape-like appearance that grow rapidly in the womb [3]. The abnormality is caused by a problem at conception, manifested by an excessive presence of placenta with little or no fetal development [10].

Hydatidiform moles are the most common form of benign gestational trophoblastic disease [4]. Often fatal in past centuries, significant medical advances in recent years now permit most women with moles to be cured [6].

Depending on the imbalance of genetic material in the pregnancy, the two major types of hydatidiform moles are classified as either complete or partial [1]. 

Forming when the sperm fertilizes an egg having no chromosomal or genetic material, a complete molar pregnancy is characterized by the presence of the placenta without an embryo [3].

 Normally, the fertilized ovum would die and not implant itself in the womb [3]. In rare instances, this egg implants, triggering the growth of the placenta and the production of human chorionic gonadotrophin (HCG), the pregnancy hormone, therefore all symptoms of pregnancy will be present [5].

Partial-molar pregnancies are formed when; a normal ovum is fertilized by two sperms [3-5]. Instead of forming twins, the excessive presence of chromosomal material and trophoblastic tissue prevents normal fetal development [3]. The fetus does not survive more than three months and dies in the uterus [5-7].

As moles are rare, epidemiological studies vary in reporting incidences [6]. Vassilakos [11] states that the frequencies of moles vary by race and occur more among Asian women. Age is a known factor as higher rates of moles occur in women over the age of 40 and under the age of 20 [4,5,8,11], as well as in women under 16 and over 50 [10].

Women with either mole type have symptoms of vaginal bleeding, nausea and vomiting, and can present hyperthyroidism or preeclampsia [1-5].

Routine first trimester ultrasound examination can identify partial or complete molar pregnancy. The most of cases present as missed pregnancy during ultrasonic examination [10]. Histopathological examinations of products of conception are presently gold standard for diagnosis of gestational molar pregnancy. Abnormally high HCG blood levels and overly large uterine size suggestive of molar pregnancy and will warrant further clinical evaluation [2].

Patients who are diagnosed with molar pregnancy must be evaluated for possible complications such as: overactive thyroid, anemia, and toxemia of pregnancy. Patients should have a complete examination and laboratory testing [6].

After any medical complications have been addressed, a decision must e 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 then methods involving induction with oxytocin or prostaglandin.  Rh immune globulin should be given to patient with RH conflict [7].

Patients are monitored to prevent the recurrence of benign moles and the development of malignant neoplasia, which can metastasize to the brain, liver or lungs [3]. Chest x-rays and the analysis of HCG levels for six months to one year are necessary [5]. Recurring moles are treated with methotrexate, a low-level chemotherapy [7].

The American College of Obstetricians and Gynecologists 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 milliliter) [9].

• Dey M, Dhawan M (2011) Critical care management of molar pregnancy in a peripheral set-up. Med J Armed Forces India 67: 385-387. [Crossref]
• Hydatidiform mole and choriocarcinoma UK information and support service. (2013, July 1). RetrievedAugust9, 2014, from http://www.hmole-chorio.org.uk/faqs.html
• HardingM (2013, October 18)Hydatidiform mole | Health | Patient.co.uk. RetrievedAugust12, 2014, from http://www.patient.co.uk/health/hydatidiform-mole
• Hernandez E (2013, 2021 Copyright OAT. All rights reservneoplasia. Retrieved August 10, 2014, from http://emedicine.medscape.com/article/279116-overview
• Hill A (2011, July 26) Molar pregnancy. Retrieved August 15, 2014, from http://www.obgyn.net/molar-pregnancy
• LurainJR (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]
• Molar pregnancy - NHS Choices (2012, September 18) RetrievedAugust9, 2014, from http://www.nhs.uk/conditions/Molar-pregnancy/Pages/Introduction.aspx
• MooreLE, HernandezE (2012, January 30)Hydatidiform mole. RetrievedAugust9, 2014, from http://emedicine.medscape.com/article/254657-overview
• Ross S, Berkowitz M, Goldstein DP (2009). Molar pregnancy. The new England Journal of Medicine, 360.
• 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
• Vassilakos,P. (2012, August 17).Pathology of molar pregnancy. RetrievedAugust9, 2014, from http://www.gfmer.ch/Books/Reproductive_health/Mole.html

Editorial Information

Editor-in-chief.

Andy Goren University of Rome "G.Marconi"

Article Type

Publication history.

Received date: August 15, 2018 Accepted date: August 23, 2018 Published date: August 29, 2018

©2018 Yuabova M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Yuabova M (2018) Molar Pregnancy-Case report. Clin Case Rep Rev 4: doi: 10.15761/CCRR.1000430.

Corresponding author

Assistant Professor, La Guardia Community College, City University of New York, NY, USA

Journal Home

• Article Info
• Author Info
• Figures & Data
• Privacy Policy
• Terms & conditions

© 2017 Copyright OAT. All rights reserved.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Case Rep Womens Health
• v.39; 2023 Sep
• PMC10587699

Cesarean scar ectopic partial molar pregnancy: A case report and a review of literature

Rania al-bataineh.

a Faculty of Medicine, Jordan University of Science & Technology, Irbid 22110, Jordan

Shireen Rawashdeh

b Faculty of Medicine, Yarmouk University, 22110 Irbid, Jordan

Leen N. Lataifeh

Saja m. alzghoul, ahmed h. al sharie, rawan obeidat.

c Department of Obstetrics & Gynecology, Faculty of Medicine, Jordan University of Science and Technology, King Abdullah University Hospital, Irbid 22110, Jordan

Omar F. Altal

A scar ectopic pregnancy exhibiting hydatidiform features is an extremely rare and clinically challenging entity. Delayed diagnosis and failure to treat such cases promptly can lead to devastating consequences. In this report, we present a case of cesarean scar ectopic partial molar pregnancy in a 37-year-old woman who presented with complaints of vaginal discharge with streaks of blood and lower abdominal pain. Diagnostic laparoscopy revealed an abnormal mass of brown soft tissue in the anterior wall of the uterus, measuring 13.0 × 9.0 × 2.0 cm, raising suspicion (in the context of elevated serum human chorionic gonadotropin levels) of a scar ectopic pregnancy. Open laparotomy was performed, and the scar ectopic mass was successfully removed. The histologic examination of the tissue revealed a partial hydatidiform mole. The patient experienced a full recovery postoperatively, with serum human chorionic gonadotropin levels gradually declining to normal values. This report is unique in its presentation of the clinicopathological features of cesarean scar ectopic molar pregnancy and the successful management of the condition.

• • Cesarean scar ectopic molar pregnancy is an extremely rare entity.
• • We present a case of cesarean scar partial molar pregnancy.
• • A mixed laparoscopic and laparotomy approach have been introduced.

1. Introduction

Cesarean scar pregnancy (CSP) is an uncommon, potentially life-threatening variant of ectopic pregnancy. It is, by definition, a pregnancy that results from implantation of the embryo into the myometrial site of a cesarean section scar [ 1 ]. Although CSPs were once considered to be extremely rare, their incidence is increasing as a consequence of the rising rates at which cesarean sections are being performed. Furthermore, the use of high-resolution ultrasound scans is increasing the number of cases being detected and hence reported [ 2 ]. According to Ouyang et al., the overall estimated incidence of CSPs is 1 per 1688 pregnancies [ 3 ]. CSP accounts for 6% of all ectopic pregnancies in women with at least one previous lower uterine segment scar [ 4 ].

Molar pregnancy is a type of gestational trophoblastic disease (GTD), where abnormal trophoblasts with a neoplastic potential implant in the uterus with an incidence of 0.6–8 per 1000 pregnancies [ 5 ]. The condition compromises two closely related but genetically different types of abnormal pregnancies: complete moles and partial moles. Both carry the potential for malignant transformation, although the risk is significantly greater for complete moles [ 5 ]. Many malignant forms arise from molar pregnancy, such as placental-site trophoblastic tumor, gestational trophoblastic neoplasia (GTN), invasive mole, choriocarcinoma and epithelioid trophoblastic tumor [ 5 ].

The concomitant occurrence of CSP and molar pregnancy is extremely rare. We describe the laparoscopic management of a patient with partial mole implanted in a cesarean section scar.

2. Case Presentation

A 37-year-old Middle Eastern woman (para 3 + 1) who had had two spontaneous vaginal deliveries, one lower transverse cesarean section (LTCS), and one miscarriage, presented to the emergency department four months after a miscarriage complaining of persistent vaginal discharge with streaks of blood and lower abdominal pain. Her medical history was remarkable for one emergency LTCS four years prior to presentation due to late decelerations and fetal distress; the surgery was uncomplicated and delivery of the baby was successful.

The patient was vitally stable. Speculum exam was unremarkable and showed a normal-looking, healthy vulva, vagina, and cervix. The serum human chorionic gonadotropin level (β-hCG) was high (43 IU/L), and the patient was anemic with a hemoglobin of 8 g/dL, a mean cell volume of 76 μm 3 , and a hematocrit of 23.8%. An ultrasound (U/S) scan was significant for a bulky uterus, with multiple fibroids, mild free fluid, with no abnormalities detected in the adnexa. However, the endometrial lining was not assessed.

The patient was started on amoxicillin/clavulanic acid and admitted for diagnostic laparoscopy (DL) for suspected ectopic versus molar pregnancy. At DL, the pelvic cavity was healthy, and both tubes and ovaries were healthy with no bleeding, but an abnormal mass of brown soft tissue was detected in the anterior wall of the uterus measuring 13.0 × 9.0 × 2.0 cm. The picture was suspicious for scar ectopic pregnancy. Dissection of the mass was attempted with resultant moderate bleeding, and a decision to proceed with open laparotomy was then taken. During the laparotomy procedure, the bladder was successfully dissected and pushed down, both ureters were checked, and the scar ectopic mass was removed completely. The uterus was then closed in two layers, hemostasis secured, and a drain was inserted. The patient was estimated to have lost 2 L of blood; she was given intraoperatively two units of packed red blood cells and two units fresh frozen plasma.

Biopsy of the removed tissue ( Fig. 1 ) showed hyalinized hydropic chorionic villi, few of which showed eccentrically trophoblastic proliferation with mild atypia (these features favor the diagnosis of a partial mole). A molar CSP diagnosis was established. Recovery after the operation was uneventful, and follow-up with serial β-hCG levels was implemented. A significant decline in β-hCG levels to less than 0.1 IU/L was observed one month after the operation.

Histopathological features of the Cesarian section scar ectopic molar pregnancy (A-H) shows hyalinized hydropic chorionic villi, few of which show eccentrically trophoblastic proliferation with mild atypia, favoring the diagnosis of a partial mole.

Due to the rarity of our case and the lack of evidence in the literature, the patient was followed every 3–6 months after the normalization of β-HCG levels. Six months after the initial presentation, the patient's follow-up did not yield any significant emerging events.

3. Discussion

The exact pathophysiology behind the development of ectopic cesarean scar pregnancies is yet to be fully understood. However, a possible mechanism is that damage to the myometrium inflicted by the cesarean incision creates microscopic tracts through which an implanting blastocyst pathologically invades [ 6 ]. In keeping with this, it was originally believed that cesarean incisions usually heal without any complications, yet, recently, some authors have described defects in cesarean scars picked up on trans-vaginal U/S that imply impaired wound healing. These are typically seen as anechoic, triangular areas. It is worth noting that 24%–88% of women with previous cesarian section have these defects and are mostly asymptomatic [ 7 ]. Despite the indefinite pathogenesis-related data, it is suggested that a short time interval between a cesarean section and a subsequent pregnancy can impede scar healing and thus contribute to scar implantation [ 6 ].

Along with the rise in the use of cesarean section in the last decade from 5 to 30% of deliveries, an increase in maternal and neonatal short- and long-term complications has been documented [ 8 ]. One of these is CSP, defined as a rare complication, where the gestational sac or trophoblasts are implanted within or on top of the cesarean scar niche, estimated to complicate 1/1800–1/2500 cesarean deliveries [ 9 ]. According to Timor-Tritsch et al., different approaches to treating CSP have been described. In their case series they adopted a conservative approach, with a combination of both intragestational sac injection and systemic methotrexate, which was deemed to be successful in the treatment of early CSP [ 10 ]. Less conservative approaches were associated with a high risk of complications, the highest being with dilatation and suction curettage (D&C), systemic methotrexate, and uterine arterial embolization (UAE). Özcan et al. reported on 50 cases of CSP, 39 of which were treated with a transabdominal U/S-guided suction curettage, and 11 using a hysterotomy; 38 and 10, women, respectively, were treated successfully, but one suffered from uterine rupture in the transabdominal U/S-guided suction curettage group, and one suffered from bladder injury in the hysterotomy group [ 11 ]. Due to the intricate nature of CSP and the individualism of each case, an agreement on a first-line treatment is yet to be reached.

GTD is a group of rare diseases related to the process of conception characterized by implantation of abnormal trophoblasts. Most GTDs are benign, but some can be malignant. Hydatidiform mole (HM or molar pregnancy) is the benign form with two types. A complete mole constitutes the majority of HM, and is the result of fertilization of an empty ovum by a haploid sperm, with a resultant karyotype of 46, XX or less commonly a 46, XY, and no fetus formation. A partial mole is the product of fertilization of a normal ovum by a sperm with double the number of paternal genetic material or by two normal sperms, with a karyotype of either 69, XXX, 69, XXY, or, rarely, a karyotype of 69, XYY, and only a part of the fetus forms [ 12 ]. Both CSP and GTD are rare, and our case combines the two in one presentation.

Literature review identified ten cases similar cases ( Table 1 ). The first case documented was back in 2006 by Wu et al. The patient was presumed to have a partial mole by U/S and serum β-hCG findings and a decision to perform a D&C under U/S guidance was taken. However, the tissue near the scar was missed and another D&C had to be done [ 13 ]. Multiple cases have been described since then, with different presentations, diagnostic methods and approaches to management. Presenting symptoms were abnormal vaginal bleeding (7 out of the 11 cases, 63%), lower abdominal pain (4 out of 11, 36%), amenorrhea (3 out of 11, 27%), and unresolving symptoms of pregnancy following a miscarriage; two patients were asymptomatic and in one case symptoms were not specified. For the diagnosis, there was an agreement on the important role played by transvaginal U/S and β-hCG levels. Some proceeded to a magnetic resonance imaging (MRI) scan to confirm the diagnosis. Management has varied between different case reports. Some cases were managed with a D&C, others with an U/S surgical suction evacuation, and some with open surgical interventions [ [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] ]. In contrast, our case was the only one with a DL approach, yielding better visualization and preparedness to treat the patient's condition. Michener and Dickinson used a different approach: they started with an intragestational sac methotrexate injection, and two months later systemic methotrexate was used for plateauing of β-hCG levels. Due to unresolved molar tissue, a hysterectomy was performed ten months after the initial presentation. [ 14 ] Bleeding control techniques prior to interventions have been suggested in a number of these case studies. Ko et al. counseled their patient about the risks of bleeding and the possibility of a UAE or a hysterectomy. They used U/S guided D&C which ended with one liter of blood loss and the need for a UAE [ 17 ]. C Ling et al. also considered the high vascularity of their patient's lesion and a UAE was performed. U/S was done to confirm decreased vascularity prior to the D&C [ 19 ]. In our case, with the laparoscopic visualization of the pelvic cavity, the CSP was easily identified; however, due to the vascularity of the mass and the resultant hemorrhage after attempted dissection, a decision to proceed with an open laparotomy was then taken and successful removal of the mass was performed.

Demographics, symptoms, diagnostic tools, and management plan of reported Cesarian section ectopic molar pregnancies.

4. Conclusion

In this report, we present the clinicopathological features of cesarian scar ectopic molar pregnancy and its successful surgical management. Physicians should be alert to the possibility of an ectopic molar pregnancy implanted on a cesarian scar, regardless of risk factors for HM. More research is needed to establish a more comprehensive approach to the diagnosis and management of these rare cases.

Contributors

Rania Al-Bataineh contributed to drafting the manuscript and undertaking the literature review.

Shireen Rawashdeh contributed to drafting the manuscript and undertaking the literature review.

Leen N. Lataifeh contributed to drafting the manuscript and undertaking the literature review.

Saja M. Alzghoul contributed to drafting the manuscript and revising the article critically for important intellectual content.

Ahmed H. Al Sharie contributed to drafting the manuscript and revising the article critically for important intellectual content.

Rawan Obeidat contributed to patient care, conception of the case report, acquiring and interpreting the data, drafting the manuscript and revising the article critically for important intellectual content.

Omar F Altal contributed to patient care, conception of the case report, acquiring and interpreting the data, drafting the manuscript and revising the article critically for important intellectual content.

All authors approved the final submitted manuscript.

No funding from an external source supported the publication of this case report.

Patient consent

Written informed consent was obtained from the patient for publication of this report and associated images.

Provenance and peer review

This article was not commissioned and was peer reviewed.

Conflict of interest statement

The authors declare that they have no conflict of interest regarding the publication of this case report.