Hydatidiform mole : prevalence and outcome

Background: Hydatidiform mole (HM) is a genetically abnormal pregnancy with malignant potential, which exists in two forms, complete (CHM) and partial hydatidform mole (PHM). The incidence rates (IR) of HM show wide geographic variations, due to differences in registration practices and methods of estimating rates. With increasingly easy access to medical care, and introduction of better diagnostic techniques, pathological pregnancies are detected at an earlier gestational age (GA). As a result of earlier detection, the presenting symptoms and clinical features originally described for second trimester molar pregnancies, are becoming less frequent and the diagnostic criteria have changed. Women with a diagnosis of HM are of childbearing age, and many are eager for a new pregnancy. The aims of this thesis were to investigate the current epidemiology and diagnostic accuracy of HM, and to evaluate pregnancy outcomes subsequent to a HM.

Methods: The study population in studies I, III and IV were all women with HM in Stockholm County 1991-2010 or subgroups thereof, and the cohort in study II was all births in Sweden 1973-2009. Study I compared the main presenting symptoms and clinical features of CHM and PHM, as well as of current CHM compared to a historic cohort. In study II, subsequent pregnancy outcomes of women with a history of HM were evaluated and compared to women with no history of HM. Incidence rates of HM, in relation to age groups and time periods, were investigated in study III. Finally, study IV examined the accuracy and the inter-rater agreement in the diagnosis of HM, by re-evaluating histological slides, and applying ancillary methods, including immunohistochemistry (IHC) and image cytometry.

Results: The overall IR of HM was 2.08/1000 deliveries and 1.48/1000 viable conceptions. A temporal increase in the IR of HM was seen, while the proportion of malignant progression remained constant. The registered number and proportion of PHM increased, and a significant overdiagnosis of PHM was demonstrated. Women with HM were diagnosed 1-2 gestational weeks earlier than previously described in Stockholm County. Vaginal bleeding was the main presenting symptom for women with CHM (57%), but less common compared to a historic cohort (84%, p<0.01). The majority (53%) of women with PHM were asymptomatic at the time of diagnosis. A maternal history of HM was associated with a lower risk of preeclampsia (PE) (OR 0.75) and a slightly increased risk of preterm birth, stillbirth and large for gestational age birth (LGA), although the risk increases were inconsistent when stratified by the relationship between the molar exposure and the rankorder of subsequent births.

Conclusion: The results indicate, that while the IR of HM is increasing, the rate of malignant progression remains constant. Women with HM are diagnosed at successively earlier gestational ages, with symptoms not differing from those of a normal miscarriage. The earlier detection also makes the histological diagnosis difficult, and ancillary diagnostic methods should be applied to avoid a misdiagnosis of HM, and potentially an undetected malignancy. Women with a history of HM can expect normal future reproductive outcomes.

List of scientific papers

I. Joneborg U, Marions L. Current clinical features of complete and partial hydatidiform mole in Sweden. J Reprod Med. 2014 Jan-Feb;59(1-2):51-5.
https://pubmed.ncbi.nlm.nih.gov/24597287

II. Joneborg U, Eloranta S, Johansson AL, Marions L, Weibull CE, Lambe M. Hydatidiform mole and subsequent pregnancy outcome: a population-based cohort study. Am J Obstet Gynecol. 2014 Dec;211(6):681.e1-7.
https://doi.org/10.1016/j.ajog.2014.06.030

III. Joneborg U, Folkvaljon Y, Papadogiannakis N, Lambe M, Marions L. Temporal trends in incidence and outcome of hydatidiform mole: a retrospective cohort study. [Submitted]

IV. Joneborg U, Marions L, Sirotkina M, Wessman S, Carlson J, Papadogiannakis N. Overdiagnosis of partial hydatidiform moles – a consequence of underutilization of ancillary diagnostic techniques? [Submitted]