Gestational trophoblastic disease (GTD)

Hydatidiform mole (MH) is a fatal disease for the fetus concerning the pathological development of the fetal egg and associated with the transformation of the chorion into cysts (protective membranes formed due to unfavorable conditions in certain life cycles, in the form of bubbles containing fluid) and the proliferation of the villi epithelium outer germinal membrane.

This pathological condition is accompanied by the following negative manifestations:

• bleeding;
• early toxicosis;
• enlargement of the uterus relative to the gestational age of the fetus.

PZ is diagnosed using a vaginal examination, ultrasound, fetal phonocardiography, and determination of the content of human chorionic gonadotropin (β-hCG).

Treatment includes techniques such as vacuum aspiration, curettage of the uterine cavity, and removal of the organ (hysterectomy).

What it is

Trophoblastic disease is a unique group of tumors of the female body, the occurrence of which is always associated with pregnancy. They can occur both during pregnancy and after its completion, regardless of the end date of pregnancy and its outcome. This could be a successful pregnancy that ended in childbirth, a spontaneous miscarriage, or an abortion at any stage of pregnancy. In this case, the period of development of the disease can range from several days to several years.

The source of trophoblastic tumors are trophoblasts - cells that surround the embryo and participate in the process of its attachment to the wall of the uterus, and then in the formation of the placenta during pregnancy. When trophoblasts multiply excessively, a tumor occurs.

The incidence of this pathology is no more than 1% of cases among all malignant diseases of the female genital organs. Women who become pregnant before age 21 or after age 35 are most prone to the disease.

A unique feature of these neoplasias is the high cure rate even in the presence of distant metastases, with most patients maintaining reproductive function after completion of treatment.

Trophoblastic tumor of the placental plane

Pathogenesis . Trophoblastic tumor of the placental plane is very rare and occurs at the site of placental implantation. The cells of this tumor infiltrate the muscular layer of the uterus, grow between smooth muscle fibers and gradually invade the myometrium and blood vessels. Histologically, the typical feature of this tumor is the absence of villous tissue and cytotrophoblast proliferation.

Symptoms and diagnosis . The most common symptom of a trophoblastic tumor of the placental plane is uterine bleeding, which can occur several months or years after a previous pregnancy. Unlike other forms of HTC, this tumor produces chronically low levels of r-hCG and human placental lactogen.

Treatment . Another distinguishing feature of placental plane trophoblastic tumor is its insensitivity to chemotherapy. But this tumor rarely metastasizes beyond the uterus, so hysterectomy is the treatment of choice for this disease.

Classification

Trophoblastic disease is a collective concept of benign and malignant tumors. The first includes a morphological change that causes:

• partial hydatidiform mole. Formed when an egg is fertilized by two sperm at once. Such an embryo contains an additional set of chromosomes, and, unfortunately, is not viable;
• complete hydatidiform mole. Formed when an egg with no chromosomes is fertilized. With further cell division, the paternal chromosomes double and become a replacement for the maternal ones, but no embryo is formed.

Complete hydatidiform mole

These benign tumors are diagnosed in 70% of patients, while with both complete and incomplete hydatidiform mole, only the proliferation of trophoblastic tissue and the transformation of chorionic villi into vesicles is observed. However, in 20% of cases, trophoblasts acquire the ability to malignize and metastasize. As malignant cells spread into surrounding tissues, they are classified as invasive hydatidiform mole, disseminated hydatidiform mole, chorionic carcinoma, trophoblastic tumor of the placental bed, and epithelioid trophoblastic tumor.

Forecast

Complete cure is possible in most cases. Only 1% of women may experience a recurrence of the disease in the future. After a second molar pregnancy, the risk of developing a third is much higher - up to 15-20%.

In rare cases, benign neoplasms become malignant. But even with this option, chemotherapy leads to complete recovery in 90% of women.

Emotional complications

Termination of pregnancy is a difficult experience. The desire to grieve and cry is completely natural and should not be suppressed. A frank conversation with loved ones is sometimes necessary to further restore mental strength. The child's father may also experience the loss very painfully. Each parent should not close themselves off, but share their feelings with each other and try to overcome difficulties together. If the period of despondency drags on, you should consult a psychologist. All fears and concerns about future pregnancies, if any are planned, should be discussed with your gynecologist. Almost all women respond well to treatment. And the next pregnancy can be interrupted by a hydatidiform mole with a very low probability.

Symptoms

A woman should be alert to the following signs:

• painless vaginal discharge mixed with blood of varying intensity and severity;
• an increase in the size of the uterus, inappropriate for the duration of pregnancy with a complete hydatidiform mole;
• reduced size of the uterus, inappropriate for the duration of pregnancy with partial hydatidiform mole;
• toxicosis in late pregnancy.

With malignant trophoblastic disease, the nature of discharge during menstruation changes. Monthly bleeding is either absent or occurs longer than usual and is profuse. Along with this, complaints appear about changes in taste preferences, nausea and dizziness - symptoms that suggest pregnancy. Often there is a dull pain in the lower abdomen associated with compression of the walls of the uterus by the tumor.

The course of the disease depends on the provoking factor. So, after a normal pregnancy that ends in childbirth or abortion, the disease develops rapidly, disrupting the recovery of the female body. If the tumor formed after an ectopic pregnancy or transformed from a hydatidiform mole, then the course of the disease is more favorable.

The clinical picture can vary significantly depending on the location of metastatic foci:

• with metastases in the lungs, hemoptysis, persistent cough, shortness of breath, and chest pain occur;
• with metastases in the vagina, a compaction is palpated through the anterior wall of the abdomen;
• with metastases in the liver, pain appears in the right hypochondrium;
• with metastases in the brain, constant headaches, nausea, convulsions and loss of consciousness are possible.

Diagnostics

After a gynecological examination, collecting anamnesis and recording complaints, the patient is sent for examination:

• First of all, the level of β-hCG in the blood serum is determined. This specific marker is produced by chorion cells after implantation of the embryo into the uterine wall, i.e. only a few days after fertilization and reaches its maximum concentration by 7-11 weeks of pregnancy, then begins to decrease. Trophoblastic disease is confirmed if the marker does not decrease after the 12th week of pregnancy or remains at a high level after its completion. The results of the analysis are relied upon for follow-up examinations and for determining further treatment tactics;
• Ultrasound of the pelvic organs - for initial confirmation of the disease;
• MRI of the pelvic organs - to clarify the location of the tumor;
• CT scan of the chest, abdominal cavity, MRI of the brain - to search for metastases;
• histological examination of all removed tissues obtained during previous surgical interventions. However, repeated biopsy of formations is not recommended, since it is associated with a high risk of complications.

Consequences and complications

If proper treatment is not carried out on time, the patient may develop severe complications.

• Malignant degeneration – formation of chorionic carcinoma , chorionepithelioma .
• Internal and uterine bleeding.
• Infertility.
• Intrauterine infections.
• Thrombosis.
• Infectious complications.
• Amenorrhea.

Stages

Depending on the extent of the process, there are 4 stages of the disease:

• Stage 1 – the tumor is limited to the uterine cavity;
• Stage 2 – the tumor spreads to the appendages, cervix and vagina;
• Stage 3 – metastases appear in the lungs;
• Stage 4 – metastases in other organs.

* interval between the end of the previous pregnancy and the start of chemotherapy;

** low levels of β-hCG can occur with a trophoblastic tumor at the placenta site.

If the score is ≤ 6, there is a low risk of developing tumor resistance; ≥ 7 points – high.

Indications for urgent medical attention

• High blood pressure.
• Heavy bleeding.
• Severe nausea and vomiting.
• Nagging pain or various pain symptoms in the uterus and appendages.

Pregnancy is a very difficult and at the same time responsible period for every woman. She must listen to what signals her body gives both for her own sake and for the future baby. Only a timely visit to a doctor is often the only opportunity to give birth to a child and maintain your own health.

Treatment

Treatment of a benign tumor is impossible without termination of pregnancy. An abortion is performed, and then the pathological tissue is removed with a vacuum aspirator. After the procedure, the level of β-hCG is monitored for a month. The woman takes blood tests weekly until she receives negative results three times in a row. Further control tests are carried out monthly throughout the year. It is important after evacuation of a hydatidiform mole to perform a chest x-ray and an ultrasound of the pelvic organs.

If the β-hCG test remains positive or a malignant tumor is detected, the patient needs to continue treatment. The patient should be referred to a specialized center that has experience and knowledge of this pathology, which is extremely important for determining the prognosis and effectiveness of therapy.

The leading method of treatment is chemotherapy, which should be started as soon as possible. The main indications for its implementation:

• stable or rising β-hCG levels after taking three blood tests seven days apart;
• elevated β-hCG levels six months after the procedure;
• detection of choriocarcinoma, placental bed tumor or epithelioid trophoblastic tumor;
• detection of metastases.

The doctor selects the recommended treatment regimen based on the history and characteristics of the tumor process, i.e. depending on the risk group for tumor resistance to chemotherapy. The risk group is determined according to the FIGO scale (2000) taking into account the examination results: less than 6 points corresponds to low risk, 7 or more points - high risk.

If the risks of relapse of the disease are minimal, then monotherapy with methotrexate is prescribed. At high risks of tumor recurrence, a combination of drugs is used, including etoposide, dactinomycin, methotrexate, vincristine and cyclophosphamide.

The number of chemotherapy cycles is determined individually and depends on the degree of decrease in β-hCG levels after each cycle. When the level of a specific marker is normalized, 2-4 cycles of chemotherapy are additionally carried out in the same regimen to consolidate the effect obtained.

If the tumor becomes resistant and there is no normalization of the marker level, then a transition to second-line antitumor drugs is required, for example, combinations such as dactinomycin, etoposide + dactinomycin + methotrexate + cisplatin or cisplatin + paclitaxel + etoposide.

In some cases, surgical treatment is resorted to, followed by adjuvant chemotherapy. The main indications for surgical intervention are:

• perforation of the uterine wall by a tumor;
• bleeding that is not amenable to conservative therapy and threatens the patient’s life;
• tumor resistance to standard chemotherapy in the absence of distant metastases;
• resistance of single metastases in the absence of a primary tumor.

Radiation therapy is used only for brain metastases.

How to treat hydatidiform mole?

Treatment for hydatidiform mole usually involves the use of existing therapy, but some cases are subject to clinical research and the use of unique methods. Additional clinical trials are helping to improve existing methods of treating the disease and developing completely new treatment approaches for hydatidiform mole. Many patients, in the hope of a complete cure, agree to participate in such studies, and most often they are successful and end with the woman’s recovery.

In standard treatment, it is customary to use only two methods: surgery and chemotherapy.

The surgical method involves removing the formation. At the doctor’s discretion, one of two types of surgery is performed:

• dilation and curettage: involve the removal of the entire contents of the uterus using vacuum equipment. The uterine walls are subject to complete scraping, which prevents the occurrence of hydatidiform moles in the future;
• the appointment of a hysterectomy indicates amputation of the uterus itself, but the ovaries are usually not removed.

Chemotherapy aims to destroy tumor cells using drugs. A course of chemotherapy involves regular use of tablets or intravenous and intramuscular administration of drugs. Drug treatment is systemic in nature, since chemical agents affect not only the tumor itself, but also the body as a whole.

When hydatidiform mole spreads to neighboring organs and tissues, radiation therapy can be used - highly effective X-rays penetrate the infected areas and eliminate cancer cells. Irradiation occurs with a special device that can influence the disease from the outside and with the help of plastic tubes inside.

Clinical treatments are based on the study of cancer cells. Modern standard forms of treatment were also part of clinical trials at one time, but are now successfully used in treatment. By agreeing to participate in clinical trials, patients receive a unique opportunity to be the first to experience the effectiveness of improved treatment methods. Often, clinical trials recruit women whose bodies have not responded to treatment. This makes it possible to test new drugs and monitor their effect on tissue and tumor development.

Prevention

After removal of a hydatidiform mole, it is necessary to monitor the level of β-hCG, as well as perform a chest x-ray and an ultrasound of the pelvic organs. After completion of treatment, β-hCG levels are determined every two weeks for the first three months, then monthly for a year. In the future, a control blood test is carried out once every two months, and after another year - once every four months.

Contraception is mandatory during the first year after β-hCG levels are normalized. Experts recommend choosing combined oral contraceptives as a method of contraception.

During pregnancy

During pregnancy, hydatidiform mole is a condition that is dangerous for the mother and lethal for the fetus. In such a situation, it is necessary to carry out surgical intervention, which excludes the continuation of pregnancy. Removal of pathologies in the early stages is carried out using conventional methods. If the uterus is very large, a minor caesarean section is performed.

According to statistics, approximately 70% of women after suffering a hydatidiform mole can carry a normal pregnancy. However, you can become pregnant after illness no earlier than two years later, and only after the doctor’s approval. At the earliest stages, an ultrasound examination should be performed.