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Frequently asked questions

Introduction


Gestational trophoblastic disease (GTD) is a rare group of disorders characterized by abnormal proliferation of trophoblastic cells following conception. Trophoblasts surround the fertilized egg and enable its implantation into the uterine wall. The placenta later develops from these cells.

The spectrum of GTD is broad, ranging from benign but premalignant molar pregnancies to malignant invasive forms. Given the rarity of these diseases, a centralized registry is essential. This allows for optimal pathological diagnosis, appropriate follow-up, and timely treatment when required. In addition, such registries provide valuable data that support ongoing research and improve our understanding of GTD.

When correctly diagnosed and treated, outcomes are excellent, with cure rates exceeding 98%.

More information on the different types of GTD and GTN can be found in the section “Information on the different types of GTDs/GTNs.”

Information on the different types of GTDs

  • Molar pregnancies
A molar pregnancy, also called a hydatidiform mole, is a rare condition, occurring in approximately 1 in 1,000 pregnancies. It develops at the time of fertilization due to a genetic imbalance, leading to uncontrolled proliferation of trophoblastic tissue. This abnormal development prevents the formation of a normal placenta and fetus and results in cystic structures. 
On ultrasound, molar pregnancies typically present with a grape-like appearance. Two distinct types of molar pregnancies are recognized:
 
  • Complete molar pregnancy

    A complete mole occurs when a sperm fertilizes an oocyte that has lost its maternal DNA. Because only one haploid set of paternal chromosomes is present, the DNA duplicates, resulting in a diploid karyotype. 
    In approximately 90% of cases, the karyotype is 46XX, while the remaining 10% are 46XY, usually of dispermic origin. As the genetic material is entirely paternal, a viable fetus cannot develop. 
    Ultrasound examination shows the absence of fetal tissue.

    Rarely, a complete mole may coexist with a normal twin pregnancy. These pregnancies frequently end in a miscarriage, with live birth of the unaffected twin occurring in only about 40% of cases.
     
  • Partial molar pregnancy

    A partial mole results from fertilization of a normal oocyte by two sperm or by a single sperm containing duplicated paternal DNA. The resulting karyotype is typically 69XXX or 69XXY. Ultrasound may initially show a fetus and placental tissue, but both are structurally abnormal. Due to these abnormalities, the pregnancy is not viable and usually ends in a miscarriage.

    In very rare cases, a twin pregnancy may occur in which only one conceptus is a partial mole. As with complete moles, these pregnancies often end in a miscarriage, with live birth of the unaffected twin in approximately 40% of cases.
     



Because both types of molar pregnancy frequently result in early miscarriage, they may remain undiagnosed. Therefore, pathological examination of tissue obtained after miscarriage is strongly recommended. 
 
  • Gestational trophoblastic neoplasia (GTN)
     
Several types of malignant gestational trophoblastic neoplasias have been identified:
 
  • Invasive mole

    Invasive moles usually arise from complete molar pregnancies and represent malignant transformation of an initially benign condition. Rarely, they may also develop after a partial mole. Approximately 15–20% of women with a complete mole and about 3% of women with a partial mole will develop an invasive mole.

    In this condition, molar tissue invades the myometrium, increasing the risk of uterine perforation. If left untreated, the disease may extend to surrounding pelvic structures. Patients typically present with abnormal uterine bleeding and abdominal pain.

     
  • Gestational choriocarcinoma

    A choriocarcinoma most commonly develops after a complete molar pregnancy (~50%), but it may also follow a non-molar miscarriage (~25%), a normal pregnancy (~22.5%), or an ectopic pregnancy (~2.5%). The incidence is estimated at 1–9 per 40,000 pregnancies. Approximately 3% of women with a complete mole and 0.5% of those with a partial mole will develop a choriocarcinoma.

    This is a highly aggressive and rapidly growing malignancy with early hematogenous spread. Despite its aggressive behavior, it is highly sensitive to chemotherapy and generally has an excellent prognosis.

    Patients often present with abnormal uterine bleeding, while other symptoms depend on metastatic sites, most commonly the lungs, liver, vagina, kidneys, or central nervous system. Elevated hCG levels, together with clinical symptoms, usually lead to the diagnosis.

     
  • Placental site trophoblastic tumor (PSTT)

    PSTT is a rare form of GTD, accounting for approximately 2% of cases. It arises from intermediate trophoblastic cells and most often follows a normal pregnancy, although cases after complete mole (16%) or non-molar abortion (13%) have been reported. Unlike other GTNs, PSTT is typically slow growing, with a long latency period between the index pregnancy and disease presentation, averaging 3.4 years.

    The tumor usually remains confined to the uterus but may invade the myometrium. Patients often present with abnormal bleeding or amenorrhea, and hCG levels are typically only mildly elevated.

    PSTT may be relatively resistant to chemotherapy. Given the frequent presence of localized disease without distant metastases, a hysterectomy may be considered in selected patients.

     
  • Epithelioid trophoblastic tumor (ETT)

    ETT is an extremely rare GTN that usually develops after a normal pregnancy, with a minority of cases occurring after a molar pregnancy (16%) or spontaneous miscarriage (16%). It is also slow growing, with a latency period that may extend for several years.

    Diagnosis is commonly made following abnormal uterine bleeding or amenorrhea. As with PSTT, hCG levels are typically lower than in other GTNs.

    ETTs may be chemoresistant, and because of frequent localized disease without distant metastases, a hysterectomy may be required in some patients.
    

Diagnosis


The diagnosis of a molar pregnancy or gestational trophoblastic neoplasia (GTN) is often challenging. Many symptoms, such as nausea, vaginal bleeding, or abdominal pain, are also common in q normal pregnancy. Several investigations may be performed to establish the diagnosis. 
 
  • Ultrasound
     
Ultrasound is the first-line imaging modality for the identification of molar pregnancy.

In cases of complete molar pregnancy, no fetal or normal placental structures are visible. The typical ultrasound appearance consists of an echogenic intrauterine mass with multiple grape-like cystic spaces, and no gestational sac is present. 
Assessment of myometrial invasion is essential, as it may predict the risk of persistent disease after curettage or disease recurrence. In addition, the uterine volume should be evaluated, as it correlates with tumor burden and contributes to risk assessment. 

In extremely rare cases, estimated at 1 in 20,000 to 100,000 pregnancies, a twin pregnancy with a normal fetus and a complete mole may occur. These pregnancies frequently result in spontaneous miscarriage, with a live birth of the unaffected twin reported in approximately 40% of cases. 

In partial molar pregnancies, fetal and placental tissue may be present, but both are abnormal and non-viable. Fetal abnormalities may include features of triploidy, hydrocephalus, cleft lip, syndactyly, or intrauterine growth restriction. The placenta often appears thickened and cystic.  

Similarly, in extremely rare cases (1 in 20,000 to 100,000 pregnancies), a twin pregnancy consisting of a normal fetus and a partial mole may be observed. As with complete moles, spontaneous miscarriage is common, with a live birth of the unaffected twin occurring in about 40% of cases. 

The sensitivity of ultrasound for detecting molar pregnancy is limited, particularly in early gestation. Consequently, both false-negative and false-positive results may occur. 
Correlation with hCG levels and histopathological examination of curettage or miscarriage tissue is therefore essential to establish a definitive diagnosis. 
 
  • hCG levels
     
Women with GTD or GTN typically have hCG levels higher than expected for the estimated gestational age. These elevated levels may explain symptoms such as severe nausea and vomiting, hypertension, or hyperthyroidism in some patients.
A GTN should be suspected in women previously diagnosed with a molar pregnancy who show rising hCG levels or an insufficient decline during follow-up. 
 
  • Histopathological examination
     
Histopathological examination is the cornerstone of the diagnosis of gestational trophoblastic disease. It provides the definitive diagnosis and allows accurate classification of trophoblastic lesions.

Consequently, all curettage specimens obtained after miscarriage should be systematically sent for histopathological examination, as molar pregnancies may be clinically and radiologically indistinguishable from non-molar miscarriages. 
When indicated, additional genetic analysis may further support the diagnosis and help differentiate between complete and partial molar pregnancies. 
Accurate and timely pathological diagnosis is essential to ensure appropriate follow-up and, when necessary, prompt initiation of treatment. This is the reason why anatomopathological review is systematically done in the Belgian registry of GTD. 

In case of ultrasound suspicion of a molar pregnancy, the following steps are recommended:
 
  • Prescribe  blood tests, including a serum total hCG measurement.
  • Inform the anesthesiologist  about the risk of hemorrhage.
  • Physical and gynecological examinations.
  • Perform  uterine evacuation by suction under ultrasound guidance.
  • Intravenous administration of a uterotonic agent (oxytocin) during suction is encouraged.
  • Anti-D prophylaxis must be administered to Rh-negative patients.

At this stage, we do not recommend any imaging-based work-up.

The diagnosis is established through pathological examination of the curettage specimen. This diagnosis must be confirmed by systematic review by the expert panel of the Belgian Registry of Gestational Trophoblastic Diseases. 
In cases of suspected partial hydatidiform mole, we recommend performing a karyotype to confirm the pathological diagnosis.

 
Diagnostic and management pathway for (first) HM. aBest practice. CXR, chest X-ray; hCG, human chorionic gonadotropin; HM, hydatidiform mole; US, ultrasound. (Lok C. et al. EOTTD-ESGO-GCIG-ISSTD Guidelines for GTD. JCO 2025.)

Complete Hydatidiform Mole
Histologically, a complete hydatidiform mole is characterized by enlarged, edematous, hydropic chorionic villi, often with cistern formation. In addition, there is a marked, usually circumferential, villous trophoblastic proliferation with cytologic atypia.

In very early complete hydatidiform moles, these characteristic histologic features may be less well developed, and trophoblastic proliferation is typically more limited.

As a rule, fetal tissues are absent.Immunohistochemically, p57 expression is absent in the villous stromal cells and the cytotrophoblast.

 
Partial Hydatidiform Mole
A partial hydatidiform mole typically demonstrates a mixed population of chorionic villi, consisting of small fibrotic villi and enlarged, irregularly shaped villi with variable degrees of edema and hydropic change. Mild to moderate circumferential trophoblastic proliferation is usually present. Cistern formation and trophoblastic pseudoinclusions are common findings.

Fetal blood vessels and nucleated red blood cells are frequently identified.Immunohistochemically, p57 expression is retained in the villous stromal cells and the cytotrophoblast.

The morphological features of a partial hydatidiform mole are not entirely specific and may show considerable overlap with those of an (early) complete hydatidiform mole, hydropic abortion, trisomy syndromes and other chromosomal abnormalities, placental mesenchymal dysplasia, and twin pregnancies with a complete hydatidiform mole coexisting with a normal fetus.

 
Gestational Choriocarcinoma
Gestational choriocarcinoma is characterized by infiltrative, destructive solid aggregates of mononuclear cytotrophoblast and intermediate trophoblast surrounded by multinucleated syncytiotrophoblast exhibiting marked cytologic atypia and high mitotic activity. 

Hemorrhage, necrosis, and lymphovascular invasion are common findings.

Gestational choriocarcinoma may occur in association with an epithelioid trophoblastic tumor and a placental site trophoblastic tumor.

 
Placental Site Trophoblastic Tumor (PSTT)
Placental site trophoblastic tumor (PSTT) consists of an infiltrative proliferation of implantation-site intermediate (extravillous) trophoblastic cells arranged in nests, cords, and diffuse aggregates infiltrating between the smooth muscle fibers of the myometrium.

The tumor cells are typically large, polygonal, and predominantly mononuclear, with abundant eosinophilic to clear cytoplasm and variable nuclear pleomorphism. Mitotic activity is generally low (1–2 mitoses/mm²).

A characteristic feature is prominent vascular invasion, in which tumor cells replace the vessel wall ("vascular remodeling"), analogous to the physiological process of implantation. Necrosis and hemorrhage may also be present.

 
Epithelioid Trophoblastic Tumor (ETT)
Epithelioid trophoblastic tumor (ETT) is a neoplasm derived from chorionic-type intermediate trophoblast. Histologically, it typically exhibits a nodular, expansile growth pattern composed of large nests and cords of relatively uniform epithelioid trophoblastic cells with well-defined cell borders.

The tumor cells are mononuclear, medium-sized, and epithelioid, with moderately eosinophilic to clear cytoplasm and a frequently squamoid (carcinoma-like) appearance. Mitotic activity is highly variable.

A characteristic feature is the presence of extracellular eosinophilic hyaline (fibrinoid) material located centrally within the nests or between the tumor cells. Extensive geographic necrosis is frequently observed.

Trophoblastic diseases are rare, which can make diagnosis, treatment, and follow-up challenging. The Belgian Registry aims to improve patient care and deepen medical understanding. 
With the patients' consent, we offer to register these conditions in collaboration with their physician, in order to document these rare diseases, monitor patient cases, and provide guidance on appropriate management.
Registration can be completed via the “Register a patient” button at the top of this page.

By participating, patients and healthcare professionals contribute to better outcomes and future advancements in care.

Together, we enhance treatment and knowledge! 

Because gestational trophoblastic diseases are rare, most gynecologists and pathologists encounter only a limited number of cases during their careers. 
Centralization of care is therefore essential to build expertise, improve knowledge of these conditions, and optimize patient management. 

Registering your patient in the national database ensures that the case is reviewed and followed by expert gynecologists and pathologists. In addition, both you and your patient will have a dedicated contact point at the reference center to support you with any questions or concerns throughout follow-up and treatment.

Registering your patient offers several direct benefits for you as the treating physician.

Registration ensures:
 
  • Expert pathological review of your patient’s diagnosis
  • Expert gynecological review of your patient’s case, ensuring optimal follow-up and, when indicated, the most appropriate treatment
  • Direct access to a reference center, providing a point of contact for any questions or concerns regarding diagnosis, follow-up, or management

Registration also provides clear benefits for your patient. 

It ensures:
 
  • Expert pathological review of her diagnosis
  • Expert gynecological review of her case, ensuring optimal follow-up and, if needed, appropriate treatment tailored to her situation
  • Direct access to the reference center, where she can obtain support and answers to questions throughout her care.

Treatment


The need for treatment depends on the exact diagnosis and the evolution of the disease. 
 
Molar pregnancy
  • Complete evacuation of the molar pregnancy is the cornerstone of treatment. Curettage is performed under ultrasound guidance to remove all trophoblastic tissue. If a curettage has already been performed following a miscarriage, repetition is usually not required.
  • A follow-up ultrasound may be performed 15 days after curettage to confirm that the uterine cavity is empty.
  • Serum hCG levels should be monitored at least every two weeks to assess whether they decrease and normalize as expected. If hCG levels normalize, no further intervention is required.
  • If hCG levels rise or plateau without normalization, or if retained molar tissue is identified on ultrasound, an additional curettage may be necessary. If no retained tissue is detected, further investigations are required to determine the most appropriate management or treatment. Advice tailored to the individual patient’s situation will be provided.
     
     
    Diagnostic pathway for (suspected) HM to GTN. aBest practice. CHM, complete hydatidiform mole; GTD, gestational trophoblastic disease; GTN, gestational trophoblastic neoplasia; hCG, human chorionic gonadotropin; HM, hydatidiform mole; PHM, partial hydatidiform moles. (Lok C. et al. EOTTD-ESGO-GCIG-ISSTD Guidelines for GTD. JCO 2025.)
     
Gestational trophoblastic neoplasia
Patients diagnosed with post-molar GTN usually require treatment. The proposed treatment is based on the WHO/FIGO risk score, which is calculated using several prognostic factors and estimates the risk of resistance to single-agent chemotherapy.
 
 

The total risk score is obtained by summing the individual scores. A score <7 defines low-risk disease, while a score ≥7 defines high-risk disease.

In the event of relapse, the risk score is recalculated based on the patient’s current situation.

This scoring system is not suitable for the management of placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT).

 
Postmole GTN staging. aBest practice. CT, computed tomography; CXR, chest X-ray; GTD, gestational trophoblastic disease; GTN, gestational trophoblastic neoplasia; hCG, human chorionic gonadotropin; MRI, magnetic resonance imaging; TFT, thyroid function test; US, ultrasound. (Lok C. et al. EOTTD-ESGO-GCIG-ISSTD Guidelines for GTD. JCO 2025.)
We strongly advise performing curettage under ultrasound guidance to ensure complete removal of tissue and to reduce the risk of uterine perforation.

As molar tissue is highly vascularized, particular care should be taken to minimize the risk of bleeding. The anesthesiologist should be informed in advance of the increased hemorrhagic risk. Oxytocin may be administered to stimulate uterine contractions and reduce blood loss.

In Rh-negative women, Rh-(D) immune globulin should be administered to prevent alloimmunization. 

Since the treatment is tailored to each individual situation it requires the opinion of an expert center. The choice is based on several factors, including the type of GTN, the age, and the medical test results of your patient. 

The first-choice treatment depends on a risk score, called “WHO/FIGO score”, of resistance to single agent chemotherapy. Low-risk diseases with a score < 7 are treated with monotherapy. High-risk diseases require treatment with multiagent chemotherapy in a specialized center.
 
1. MEDICAL TREATMENT
The most used medical treatment schedules are: 

Methotrexate (MTX)
  • Administered by intramuscular injection on days 1, 3, 5 and 7
  • Folinic acid (leucovorin) orally on days 2, 4, 6 and 8 (24–30 hours after MTX) to reduce side effects, mainly nausea, vomiting and mouth sores
  • Treatment is repeated every 2 weeks until hCG levels normalize, followed by at least two mandatory consolidation cycles
  • Depending on the anticipated risk for bleeding it might that your patient is hospitalized for the first dosing(s) 
     
EMA-CO
  • This schedule consists of a combination of several medications:
     
 
  • Treatment is repeated every 2 weeks until hCG levels normalize, followed by at least two mandatory consolidation cycles
  • Depending on the guidelines of the treatment center the patient might be hospitalized during treatment

Other treatment schedules might be proposed to your patient, based on her situation. If so, the reference center will discuss these with you in more detail.
 
 
2. SURGICAL TREATMENT
 
  • Second curettage: may be considered if residual trophoblastic tissue is seen on ultrasound; cure rate for GTN of approximately 40%.
  • Hysterectomy: an alternative treatment in women who have completed childbearing and have disease confined to the uterus.
     
Please feel free to contact us if you have any questions about the treatment of your patient. 

 
Postmole GTN treatment. aBest practice. FIGO, International Federation of Gynecology and Obstetrics; GTD, gestational trophoblastic disease; GTN, gestational trophoblastic neoplasia; MDT, multidisciplinary team. (Lok C. et al. EOTTD-ESGO-GCIG-ISSTD Guidelines for GTD. JCO 2025.)
 
High-risk GTN treatment to remission. aBest practice. bMost often used, but other multichemotherapy schedules are possible, reassuring on fertility; in selected cases, referral to the fertility specialist might be appropriate. cEvidence uncertain. CO, cyclophosphamide and vincristine; CT, computed tomography; EMA, etoposide, MTX, and actinomycin-D; EP, etoposide and cisplatin; FIGO, International Federation of Gynecology and Obstetrics; GTD, gestational trophoblastic disease; GTN, gestational trophoblastic neoplasia; hCG, human chorionic gonadotropin; IT-MTX, intrathecal MTX; MRI, magnetic resonance imaging; MTX, methotrexate. (Lok C. et al. EOTTD-ESGO-GCIG-ISSTD Guidelines for GTD. JCO 2025.)

The possible side effects depend on the type of treatment that your patient receives. Not all patients experience side effects, and their intensity can vary.

Some side effects that may occur with different treatments include:
 
  • Low white blood cell count (neutropenia) – In case of neutrophils <1.5 * 109/L you should consider to postpone the start of a new cycle. Neupogen will be administered until the neutrophils recover. Afterwards Neupogen should be administered prophylactically weekly on day 5 and, if necessary, on day 12.
  • Low platelet count (thrombocytopenia) – In case of thrombocytes <100 * 109/L you should consider postponing the start of a new cycle.
  • Nausea and vomiting
  • Mouth sores – good mouth hygiene and a stomatitis cocktail are strongly advised.
  • Fatigue
  • Liver or kidney effects – Salicylates and NSAIDs should be avoided.
  • Lung inflammation (pneumonitis) – please be aware of dyspnea or breathing difficulties.
  • Conjunctivitis – Consider ophthalmologic flushing with Leucovorin (15ml in 30ml NaCl 0.9%) two to three times per day.
  • Alopecia

The regular premedication is required, including IV hydration to avoid kidney toxicity, when cisplatin is used. 

If, during treatment, hCG levels increase or stop decreasing without returning to normal, this means that the treatment is not having the desired effect.

In this situation, a different treatment will be proposed.  

Please feel free to contact the responsible person in your reference center in case you have questionsregarding the treatment of your patient. 

The contact persons for the Flemish reference center are:
Tine Op de beeck                  016/342 923           tine.opdebeeck@uzleuven.be
Ellen Reynders                        016/342 996           ellen.reynders@uzleuven.be
Joke De Roover                      016/347 419           joke.deroover@uzleuven.be

The contact persons for the French reference center are:
Frédéric Goffin                       info-fr@mole-chorio.be / fgoffin@chuliege.be
Sophie Schoenen                   info-fr@mole-chorio.be / s.schoenen@chuliege.be
Christelle Leclercq                 04/321.65.10 – 04/321.36.72  

Follow-up


You should advise your patient to adhere strictly to the recommended follow-up schedule. Monitoring hCG levels is essential for proper disease surveillance. An increase in hCG levels, or stabilization without normalization, indicates either persistent molar tissue or progression to gestational trophoblastic neoplasia (GTN). 
In both situations, further evaluation is required to identify the cause and initiate the most appropriate treatment. Guidance tailored to your patient’s specific situation will be provided.

In rare cases, false-positive hCG results may occur due to cross-reactivity with heterophilic antibodies. This should be considered particularly in patients receiving chemotherapy who show persistently low but stable hCG levels without normalization or in patients with a molar pregnancy whose hCG levels plateau below 50 IU/L. As heterophilic antibodies are not excreted in urine, a urinary hCG test is usually helpful to clarify the diagnosis.

In a normal pregnancy, the hormone hCG (human chorionic gonadotropin) is mainly present in its intact “beta” form, which is the one detected by standard pregnancy tests. 

In molar pregnancies or gestational trophoblastic diseases (GTN), however, the body produces several different forms of hCG — including fragmented or less glycosylated variants. Because standard tests are designed to detect only the usual form seen in normal pregnancies, they can sometimes give false-negative results in these diseases. 

To ensure reliable monitoring, we therefore measure total hCG, which includes all molecular forms of the hormone. It is also very important that all the blood samples are analyzed in the same laboratory, using the same test method and detection threshold, so that the results can be accurately compared over time. 

In certain situations, a urine sample for hCG testing can be necessary. This can help confirm the results if we suspect that serum antibodies are interfering with the test, since such antibodies are not present in urine. 
  • Partial mole 
A blood test at your usual laboratory is required at least once every two weeks until hCG levels normalize (threshold varies depending on the laboratory). 
This normalization must be confirmed by at least one test within the month following normalization. This concludes the monitoring of a partial mole. In some cases, eg. when the hCG normalization took more than 8 weeks, a longer follow-up might be advised. 
 
  • Complete mole
A blood test at your usual laboratory is recommended at least once every two weeks until hCG levels normalize (threshold varies depending on your laboratory). 
After normalization, monthly tests will be performed for a duration of 6 months. 
 
  • Gestational trophoblastic neoplasia 
Follow-up after GTN is different from follow-up after a molar pregnancy. 

Low-risk diseases 
In low-risk gestational trophoblastic neoplasia (GTN), once the hCG level has returned to normal, regular follow-up is recommended for at least one year, with monthly blood tests. 
Any remaining findings seen on imaging tests (such as ultrasound or scans) do not need further treatment as long as the hCG level remains normal. 
The risk of the disease coming back is low, but it can vary depending on the original diagnosis (the risk is slightly higher after choriocarcinoma) and on whether lung involvement was present at the time of diagnosis. 
If a recurrence does occur, it most often happens within the first year, which is why close follow-up during this period is important. After a subsequent pregnancy, the hCG should have normalized within 6 weeks and a repeat hCG is recommended at this time to ensure no reactivation of GTN. 

High-risk diseases 
Protocols for hCG follow-up varied in frequency and duration between GTD centers. However, consensus was reached to monitor the hCG at least monthly for a year or more (generally 18 months) after 4-8 weeks of normal hCG values and completion of treatment. 
After a subsequent pregnancy, the hCG should have normalized within 6 weeks and a repeat hCG is recommended at this time to ensure no reactivation of GTN. 

Your patient needs to use contraception to avoid becoming pregnant from the time of the curettage until the end of the follow-up period. This is important to allow reliable monitoring of hCG levels. 

In most cases, you will prescribe an oral contraceptive pill. 

In case of medical contraindications to oral contraceptives or wish of a different method of contraception, you can discuss safe and effective alternative options with your patient. For example, an intrauterine contraceptive device (IUCD) can be inserted once uterine vacuity is checked.

Even after normalization of hCG levels, relapses cannot be completely excluded. As most recurrences occur within the first months after hCG normalization, patients are required to observe a defined follow-up period. During this time, effective contraception should be used and regular hCG monitoring continued. 

The duration of the follow-up period depends on the patient’s specific diagnosis. Further details are provided in the section “When can my patient become pregnant again?”. 

A new pregnancy leads to renewed hCG production and may therefore mask disease recurrence, resulting in delayed diagnosis and potentially reducing the effectiveness or simplicity of treatment.

A new pregnancy is usually permitted as soon as hCG normalization is confirmed after a partial molar pregnancy. In some cases, eg. when the hCG normalization took more than 8 weeks, a longer follow-up, and thus a longer delay of a next pregnancy, might be advised. 

For complete molar pregnancies, a waiting period of 6 months is required, during which hCG levels are monitored monthly.
 
  • If the hCG normalization occurs within 8 weeks after the first curettage, the waiting period is 6 months from the date of curettage.
  • If the hCG normalization occurs more than 8 weeks after the first curettage, the waiting period is 6 months from hCG normalization.
     
For gestational trophoblastic neoplasia, a waiting period of 12 to 18 months after hCG normalization and completion of chemotherapy is generally recommended. However, each case should be individually evaluated by an expert center to ensure optimal management.
Both you and your patient are welcome to contact the designated person at the reference center with any questions regarding the diagnosis, follow-up, or treatment of a molar pregnancy or GTN. 

The contact persons for the Flemish reference center are:
Tine Op de beeck                  016/342 923           tine.opdebeeck@uzleuven.be
Ellen Reynders                        016/342 996           ellen.reynders@uzleuven.be
Joke De Roover                      016/347 419           joke.deroover@uzleuven.be

The contact persons for the French reference center are:
Frédéric Goffin                       info-fr@mole-chorio.be / fgoffin@chuliege.be
Sophie Schoenen                   info-fr@mole-chorio.be / s.schoenen@chuliege.be
Christelle Leclercq                 04/321.65.10 – 04/321.36.72 

Future implications


Even after normalization of hCG levels, a relapse cannot be completely excluded. As most recurrences occur within the first months after hCG normalization, patients are required to observe a defined follow-up period. During this time, effective contraception should be used and regular hCG monitoring continued. 

The duration of the follow-up period depends on the patient’s specific diagnosis. Further details are provided in the section “When can my patient become pregnant again?”. 

A new pregnancy leads to renewed hCG production and may therefore mask disease recurrence, resulting in delayed diagnosis and potentially reducing the effectiveness or simplicity of treatment.

A new pregnancy is usually permitted as soon as hCG normalization is confirmed after a partial molar pregnancy. In some cases, eg. when the hCG normalization took more than 8 weeks, a longer follow-up, and thus a longer delay of a next pregnancy, might be advised. 

For complete molar pregnancies, a waiting period of 6 months is required, during which hCG levels are monitored monthly.
  • If the hCG normalization occurs within 8 weeks after the first curettage, the waiting period is 6 months from the date of the curettage.
  • If the hCG normalization occurs more than 8 weeks after the first curettage, the waiting period is 6 months from the date of the hCG normalization.
     
For gestational trophoblastic neoplasia, a waiting period of 12 to 18 months after hCG normalization and completion of chemotherapy is generally recommended. However, each case should be individually evaluated by an expert center to ensure optimal management.

The different chemotherapy regimens do not affect fertility and do not increase the risk of congenital abnormalities. However, we strongly recommend that patients wait at least one year before attempting a new pregnancy. This allows the follow-up of hCG levels and the body to fully eliminate the treatment and recover sufficiently to support a future pregnancy under optimal conditions. We encourage you to emphasize the importance of respecting this waiting period to your patient. 

Some treatment-related side effects may be long-term or even permanent. This is particularly the case for neuropathy, which may occur with paclitaxel. Although gradual improvement is often observed in the months following completion of treatment, symptoms may not fully resolve. 

Paclitaxel, etoposide, and actinomycin may also cause alopecia. When the hair regrows, changes in texture may be observed. These changes can sometimes be permanent. 

Most long-term side effects of chemotherapy are uncommon. When they occur, they are usually mild and manageable. Please do not hesitate to contact us if you or your patient have any questions regarding persistent side effects.

After one molar pregnancy, your patient has approximately 1% risk of developing another molar pregnancy, which is 10 to 20 times higher than the risk in the general population (1/1000). This estimate applies regardless of whether the patient previously developed a neoplasia. If your patient has had two or more prior molar pregnancies, the risk of a subsequent molar pregnancy increases to 15–20%. Genetic testing may be indicated if a second molar pregnancy occurs or if your patient has a family history. 

In the case of a GTN, most recurrences represent relapse of the same neoplastic process rather than the development of a new, independent GTN, and these relapses typically occur within the first year after treatment, rather than many years later. While precise estimates for the risk of a second independent GTN after a first GTN are not well defined in the literature, the available data indicate that the risk remains higher than baseline but low in absolute terms. Close hCG surveillance and expert management are therefore essential to mitigate this risk.

There is no international consensus on this topic. However, we recommend an early ultrasound examination in any future pregnancy to confirm the presence of a normal, viable fetus. 

If no viable fetus is identified, histopathological examination of curettage tissue is recommended.

Only a very small percentage of women have a familial predisposition to recurrent molar pregnancies. This rare condition is known as familial recurrent hydatidiform mole (FRHM). 

Women affected by FRHM almost exclusively develop complete molar pregnancies. Unlike typical complete moles, which contain only paternal chromosomes, these moles are of biparental origin. Further characterization has identified NLRP7 and KHDC3L as the most frequently mutated genes in FRHM, accounting for approximately 75–80% and 5–10% of cases, respectively. Both genes play a key role in maternal imprinting during oogenesis and early embryonic development. Due to these defects, DNA methylation follows a paternal rather than maternal pattern, highlighting the importance of imprinting in early normal pregnancy development. 

As FRHM is an autosomal recessive disorder, affected women generally require oocyte donation to achieve a successful pregnancy. 

Genetic counselling is indicated if your patient is diagnosed with a second or subsequent GTD, or if she reports a family history of molar pregnancies.
Please feel free to contact the responsible person in your reference center in case you need support after the diagnosis of a molar pregnancy or a GTN. 

The contact persons for the Flemish reference center are:
Tine Op de beeck                  016/342 923           tine.opdebeeck@uzleuven.be
Ellen Reynders                        016/342 996           ellen.reynders@uzleuven.be
Joke De Roover                      016/347 419           joke.deroover@uzleuven.be

The contact persons for the French reference center are:
Frédéric Goffin                     info-fr@mole-chorio.be / fgoffin@chuliege.be
Sophie Schoenen                 info-fr@mole-chorio.be / s.schoenen@chuliege.be
Christelle Leclercq               04/321.65.10 – 04/321.36.72