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Treatment is always necessary.
The treatment for hydatidiform mole consists of the evacuation of pregnancy. Evacuation will lead to the relief of symptoms, and also prevent later complications. Suction curettage is the preferred method of evacuation. Hysterectomy is an alternative if no further pregnancies are wished for by the female patient. Hydatidiform mole also has successfully been treated with systemic (intravenous) methotrexate.
The treatment for invasive mole or choriocarcinoma generally is the same. Both are usually treated with chemotherapy. Methotrexate and dactinomycin are among the chemotherapy drugs used in GTD. Only a few women with GTD suffer from poor prognosis metastatic gestational trophoblastic disease. Their treatment usually includes chemotherapy. Radiotherapy can also be given to places where the cancer has spread, e.g. the brain.
Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment. These women also are likely to have an earlier menopause. It has been estimated by the Royal College of Obstetricians and Gynaecologists that the age at menopause for women who receive single agent chemotherapy is advanced by 1 year, and by 3 years for women who receive multi agent chemotherapy.
Hydatidiform moles should be treated by evacuating the uterus by uterine suction or by surgical curettage as soon as possible after diagnosis, in order to avoid the risks of choriocarcinoma. Patients are followed up until their serum human chorionic gonadotrophin (hCG) level has fallen to an undetectable level. Invasive or metastatic moles (cancer) may require chemotherapy and often respond well to methotrexate. As they contain paternal antigens, the response to treatment is nearly 100%. Patients are advised not to conceive for half a year after hCG levels have normalized. The chances of having another molar pregnancy are approximately 1%.
Management is more complicated when the mole occurs together with one or more normal fetuses.
The uterine curettage is generally done under the effect of anesthesia, preferably spinal anesthesia in hemodynamically stable patients. The advantages of spinal anesthesia over general anesthesia include ease of technique, favorable effects on the pulmonary system, safety in patients with hyperthyroidism and non-tocolytic pharmacological properties. Additionally, by maintaining patient’s consciousness one can diagnose the complications like uterine perforation, cardiopulmonary distress and thyroid storm at an earlier stage than when the patient is sedated or is under general anesthesia.
The term «persistent trophoblastic disease» (PTD) is used when after treatment of a molar pregnancy, some molar tissue is left behind and again starts growing into a tumour. Although PTD can spread within the body like a malignant cancer, the overall cure rate is nearly 100%.
In the vast majority of patients, treatment of PTD consist of chemotherapy. Only about 10% of patients with PTD can be treated successfully with a second curettage.
Treatment may be delivery by caesarean section and abdominal hysterectomy if placenta accreta is diagnosed before birth. Oxytocin and antibiotics are used for post-surgical management. When there is partially separated placenta with focal accreta, best option is removal of placenta. If it is important to save the woman's uterus (for future pregnancies) then resection around the placenta may be successful. Conservative treatment can also be uterus sparing but may not be as successful and has a higher risk of complications.
Techniques include:
- Leaving the placenta in the uterus and curettage of uterus. Methotrexate has been used in this case.
- Intrauterine balloon catheterisation to compress blood vessels
- Embolisation of pelvic vessels
- Internal iliac artery ligation
- Bilateral uterine artery ligation
In cases where there is invasion of placental tissue and blood vessels into the bladder, it is treated in similar manner to abdominal pregnancy and manual placental removal is avoided. However, this may eventually need hysterectomy and/or partial cystectomy.
If the patient decides to proceed with a vaginal delivery, blood products for transfusion and an anesthesiologist are kept ready at delivery.
Since gestational choriocarcinoma (which arises from a hydatidiform mole) contains paternal DNA (and thus paternal antigens), it is exquisitely sensitive to chemotherapy. The cure rate, even for metastatic gestational choriocarcinoma, is around 90–95%.
At present, treatment with single-agent methotrexate is recommended for low-risk disease, while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclosphosphamide and vincristine (Oncovin) are recommended for intermediate or high-risk disease.
Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. It may be required for those with severe infection and uncontrolled bleeding.
Choriocarcinoma arising in the testicle is rare, malignant and highly resistant to chemotherapy. The same is true of choriocarcinoma arising in the ovary. Testicular choriocarcinoma has the worst prognosis of all germ-cell cancers.
There is no effective pharmacological treatment for retained placenta. It is useful ensuring the bladder is empty. However, ergometrine should not be given as it causes tonic uterine contractions which may delay placental expulsion. Controlled cord traction has been recommended as a second alternative after more than 30 minutes have passed after stimulation of uterine contractions, provided the uterus is contracted. Manual extraction may be required if cord traction also fails, or if heavy ongoing bleeding occurs. Very rarely a curettage is necessary to ensure that no remnants of the placenta remain (in rare conditions with very adherent placenta such as a placenta accreta).
However, in birth centers and attended home birth environments, it is common for licensed care providers to wait for the placenta's birth up to 2 hours in some instances.
The first step in management of uterine atony is uterine massage. The next step is pharmacological therapies, the first of which is oxytocin, used because it initiates rhythmic contractions of the uterus, compressing the spiral arteries which should reduce bleeding. The next step in the pharmacological management is the use of methylergometrine, which is an ergot derivative, much like that use in the abortive treatment of migraines. Its side effect of hypertension means its use should not be used in those with hypertension or pre-eclampsia. In those with hypertension, the use of prostaglandin F is indicated (but beware of its use in patients with asthma).
Another option Carbetocin and Carboprost where Oxytocin and ergometrin is inappropriate.
Women with benign germ cell tumors such as mature teratomas (dermoid cysts) are cured by ovarian cystectomy or oophorectomy. In general, all patients with malignant germ cell tumors will have the same staging surgery that is done for epithelial ovarian cancer. If the patient is in her reproductive years, an alternative is unilateral salpingoophorectomy, while the uterus, the ovary, and the fallopian tube on the opposite side can be left behind. This isn't an option when the cancer is in both ovaries. If the patient has finished having children, the surgery involves complete staging including salpingoophorectomy on both sides as well as hysterectomy.
Most patients with germ cell cancer will need to be treated with combination chemotherapy for at least 3 cycles. The chemotherapy regimen most commonly used in germ cell tumors is called PEB (or BEP), and consists of bleomycin, etoposide, a platinum-based antineoplastic (cisplatin).
Ideally the management of abdominal pregnancy should be done by a team that has medical personnel from multiple specialties. Potential treatments consist of surgery with termination of the pregnancy (removal of the fetus) via laparoscopy or laparotomy, use of methotrexate, embolization, and combinations of these. Sapuri and Klufio indicate that conservative treatment is also possible if the following criteria are met: 1. there are no major congenital malformations; 2. the fetus is alive; 3. there is continuous hospitalization in a well-equipped and well-staffed maternity unit which has immediate blood transfusion facilities; 4. there is careful monitoring of maternal and fetal well being; and 5. placental implantation is in the lower abdomen away from the liver and spleen. The choice is largely dictated by the clinical situation. Generally, treatment is indicated when the diagnosis is made; however, the situation of the advanced abdominal pregnancy is more complicated.
The uterus should be evacuated and contractions should be stimulated using intravenous oxytocin; hysterectomy (the removal of the uterus) may be needed in some cases.
An initial assessment to determine the status of the mother and fetus is required. Although mothers used to be treated in the hospital from the first bleeding episode until birth, it is now considered safe to treat placenta previa on an outpatient basis if the fetus is at less than 30 weeks of gestation, and neither the mother nor the fetus are in distress. Immediate delivery of the fetus may be indicated if the fetus is mature or if the fetus or mother are in distress. Blood volume replacement (to maintain blood pressure) and blood plasma replacement (to maintain fibrinogen levels) may be necessary.
Corticosteroids are indicated at 24–34 weeks gestation, given the higher risk of premature birth.
Fertility may sometimes be restored by removal of adhesions, depending on the severity of the initial trauma and other individual patient factors. Operative hysteroscopy is used for visual inspection of the uterine cavity during adhesion dissection (adhesiolysis). However, hysteroscopy is yet to become a routine gynaecological procedure and only 15% of US gynecologists perform office hysteroscopy {Isaacson, 2002}. Adhesion dissection can be technically difficult and must be performed with care in order to not create new scars and further exacerbate the condition. In more severe cases, adjunctive measures such as laparoscopy are used in conjunction with hysteroscopy as a protective measure against uterine perforation. Microscissors are usually used to cut adhesions. Electrocauterization is not recommended.
As IUA frequently reform after surgery, techniques have been developed to prevent recurrence of adhesions. Methods to prevent adhesion reformation include the use of mechanical barriers (Foley catheter, saline-filled Cook Medical Balloon Uterine Stent, IUCD) and gel barriers (Seprafilm, Spraygel, autocrosslinked hyaluronic acid gel Hyalobarrier) to maintain opposing walls apart during healing {Tsapanos, 2002}; {Guida, 2004};{Abbott, 2004}, thereby preventing the reformation of adhesions. Antibiotic prophylaxis is necessary in the presence of mechanical barriers to reduce the risk of possible infections. A common pharmacological method for preventing reformation of adhesions is sequential hormonal therapy with estrogen followed by a progestin to stimulate endometrial growth and prevent opposing walls from fusing together {Roge, 1996}. However, there have been no randomized controlled trials (RCTs) comparing post-surgical adhesion reformation with and without hormonal treatment and the ideal dosing regimen or length of estrogen therapy is not known. The absence of prospective RCTs comparing treatment methods makes it difficult to recommend optimal treatment protocols. Furthermore, diagnostic severity and outcomes are assessed according to different criteria (e.g. menstrual pattern, adhesion reformation rate, conception rate, live birth rate). Clearly, more comparable studies are needed in which reproductive outcome can be analysed systematically.
Follow-up tests (HSG, hysteroscopy or SHG) are necessary to ensure that adhesions have not reformed. Further surgery may be necessary to restore a normal uterine cavity.
According to a recent study among 61 patients, the overall rate of adhesion recurrence was 27.9% and in severe cases this was 41.9%. Another study found that postoperative adhesions reoccur in close to 50% of severe AS and in 21.6% of moederate cases. Mild IUA, unlike moderate to severe synechiae, do not appear to reform.
Treatment depends on the amount of blood loss and the status of the fetus. If the fetus is less than 36 weeks and neither mother or fetus is in any distress, then they may simply be monitored in hospital until a change in condition or fetal maturity whichever comes first.
Immediate delivery of the fetus may be indicated if the fetus is mature or if the fetus or mother is in distress. Blood volume replacement to maintain blood pressure and blood plasma replacement to maintain fibrinogen levels may be needed. Vaginal birth is usually preferred over Caesarean section unless there is fetal distress. Caesarean section is contraindicated in cases of disseminated intravascular coagulation. People should be monitored for 7 days for postpartum hemorrhage. Excessive bleeding from uterus may necessitate hysterectomy. The mother may be given Rhogam if she is Rh negative.
The method of delivery is determined by clinical state of the mother, fetus and ultrasound findings. In minor degrees (traditional grade I and II), vaginal delivery is possible. RCOG recommends that the placenta should be at least 2 cm away from internal os for an attempted vaginal delivery. When a vaginal delivery is attempted, consultant obstetrician and anesthetists are present in delivery suite. In cases of fetal distress and major degrees (traditional grade III and IV) a caesarean section is indicated. Caesarian section is contraindicated in cases of disseminated intravascular coagulation. An obstetrician may need to divide the anterior lying placenta. In such cases, blood loss is expected to be high and thus blood and blood products are always kept ready. In rare cases, hysterectomy may be required.
The 1997 International Germ Cell Consensus Classification is a tool for estimating the risk of relapse after treatment of malignant germ cell tumor.
A small study of ovarian tumors in girls reports a correlation between cystic and benign tumors and, conversely, solid and malignant tumors. Because the cystic extent of a tumor can be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most appropriate surgical plan to minimize risk of spillage of a malignant tumor.
Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with non-seminomatous (non-germinomatous) germ cell tumors diagnosed between 1975 and 1989, 5-year survival increased over time and with earlier diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a cancer unit that treated the majority of these men, even though the unit treated more men with the worst prognosis.
Choriocarcinoma of the testicles has the worst prognosis of all germ cell cancers
It is recommended that women with vasa previa should deliver through elective cesarean prior to rupture of the membranes. Given the timing of membrane rupture is difficult to predict, elective cesarean delivery at 35–36 weeks is recommended. This gestational age gives a reasonable balance between the risk of death and that of prematurity. Several authorities have recommended hospital admission about 32 weeks. This is to give the patient proximity to the operating room for emergency delivery should the membranes rupture. Because these patients are at risk for preterm delivery, it is recommended that steroids should be given to promote fetal lung maturation. When bleeding occurs, the patient goes into labor, or if the membranes rupture, immediate treatment with an emergency caesarean delivery is usually indicated.
Small chorangiomas are not treated. Large chorangioma can be treated several ways, including chemical ablation and laser coagulation.
Intravenous oxytocin is the drug of choice for postpartum hemorrhage. Ergotamine may also be used.
Oxytocin helps the uterus to contract quickly and the contractions to last for longer. It is the first line treatment for PPH when its cause is the uterus not contracting well. A combination of syntocinon and ergometrine is commonly used as part of active management of the third stage of labour. This is called syntometrine. Syntocinon alone lowers the risk of PPH. Based on limited research available it is unclear whether syntocinon or syntometrine is most effective in preventing PPH but adverse effects are worse with syntometrine making syntocinon a more attractive option. Ergometrine also has to be kept cool and in a dark place so that it is safe to use. It does reduce the risk of PPH by improving the tone of the uterus when compared with no treatment however it has to be used with caution due to its effect raising blood pressure and causing worse after pains.
More research would be useful in determining the best doses of ergometrine, and syntocinon.
The difficulty using oxytocin is that it needs to be kept below a certain temperature which requires resources such as fridges which are not always available particularly in low-resourced settings. When oxytocin is not available, misoprostol can be used. Misoprostol does not need to be kept at a certain temperature and research into its effectiveness in reducing blood loss appears promising when compared with a placebo in a setting where it is not appropriate to use oxytocin. Misoprostol can cause unpleasant side effects such as very high body temperatures and shivering. Lower doses of misoprostol appear to be safer and cause less side effects.
Giving oxytocin in a solution of saline into the umbilical vein is a method of administering the drugs directly to the placental bed and uterus. However quality of evidence around this technique is poor and it is not recommended for routine use in the management of the third stage. More research is needed to ascertain whether this is an effective way of administering uterotonic drugs. As a way of treating a retained placenta, this method is not harmful but has not been shown to be effective.
Carbetocin compared with oxytocin produced a reduction in women who needed uterine massage and further uterotonic drugs for women having caesarean sections. There was no difference in rates of PPH in women having caesarean sections or women having vaginal deliveries when given carbetocin. Carbetocin appears to cause less adverse effects. More research is needed to find the cost effectiveness of using carbetocin.
Tranexamic acid, a medication to promote blood clotting, may also be used to reduce bleeding and blood transfusions in low-risk women, however evidence as of 2015 was not strong. A 2017 trial found that it decreased the risk of death from bleeding from 1.9% to 1.5% in women with postpartum bleeding. The benefit was greater when the medication was given within three hours.
In some countries, such as Japan, methylergometrine and other herbal remedies are given following the delivery of the placenta to prevent severe bleeding more than a day after the birth. However, there is not enough evidence to suggest that these methods are effective.
Uterine massage is a simple first line treatment as it helps the uterus to contract to reduce bleeding. Although the evidence around the effectiveness of uterine massage is inconclusive, it is common practice after the delivery of the placenta.
Placental site trophoblastic tumor is a form of gestational trophoblastic disease, which is thought to arise from intermediate trophoblast.
It may secrete human placental lactogen (human chorionic somatomammotropin), and result in a false-positive pregnancy test.
Placental site trophoblastic tumor is a monophasic neoplasm of the implantation site intermediate trophoblast, and usually a benign lesion, which comprises less than 2% of all gestational trophoblastic proliferations. Preceding conditions include molar pregnancy (5%). Compared to choriocarcinoma or invasive mole, hemorrhage is less conspicuous and serum β-HCG level is low, making early diagnosis difficult.
Immunohistochemistry: Often stains with hPL, keratin, Mel-CAM, EGFR.
Prognosis: 10–20% of cases metastase leading to death.
Treatment: Because chemotherapy is ineffective; the patient should undergo hysterectomy.
A 2013 review concluded that there were no studies reporting on the link between intrauterine adhesions and long-term reproductive outcome after miscarriage, while similar pregnancy outcomes were reported subsequent to surgical management (e.g. D&C), medical management or conservative management (that is, watchful waiting). There is an association between surgical intervention in the uterus and the development of intrauterine adhesions, and between intrauterine adhesions and pregnancy outcomes, but there is still no clear evidence of any method of prevention of adverse pregnancy outcomes.
In theory, the recently pregnant uterus is particularly soft under the influence of hormones and hence, easily injured. D&C (including dilation and curettage, dilation and evacuation/suction curettage and manual vacuum aspiration) is a blind, invasive procedure, making it difficult to avoid endometrial trauma. Medical alternatives to D&C for evacuation of retained placenta/products of conception exist including misoprostol and mifepristone. Studies show this less invasive and cheaper method to be an efficacious, safe and an acceptable alternative to surgical management for most women. It was suggested as early as in 1993 that the incidence of IUA might be lower following medical evacuation (e.g. Misoprostol) of the uterus, thus avoiding any intrauterine instrumentation. So far, one study supports this proposal, showing that women who were treated for missed miscarriage with misoprostol did not develop IUA, while 7.7% of those undergoing D&C did. The advantage of misoprostol is that it can be used for evacuation not only following miscarriage, but also following birth for retained placenta or hemorrhaging.
Alternatively, D&C could be performed under ultrasound guidance rather than as a blind procedure. This would enable the surgeon to end scraping the lining when all retained tissue has been removed, avoiding injury.
Early monitoring during pregnancy to identify miscarriage can prevent the development of, or as the case may be, the recurrence of AS, as the longer the period after fetal death following D&C, the more likely adhesions may be to occur. Therefore, immediate evacuation following fetal death may prevent IUA.
The use of hysteroscopic surgery instead of D&C to remove retained products of conception or placenta is another alternative that could theoretically improve future pregnancy outcomes, although it could be less effective if tissue is abundant. Also, hysteroscopy is not a widely or routinely used technique and requires expertise.
There is no data to indicate that suction D&C is less likely than sharp curette to result in Asherman's. A recent article describes three cases of women who developed intrauterine adhesions following manual vacuum aspiration.
True cervical pregnancies tend to abort; if, however, the pregnancy is located higher in the canal and the placenta finds support in the uterine cavity it can go past the first trimester. With the placenta being implanted abnormally extensive vaginal bleeding can be expected at time of delivery and placental removal. While early cervical pregnancies may abort spontaneously or can be managed with excision, D&C, suturing, electrocautery, and tamponading, by medication such as methotrexate, and/or by uterine artery embolization, a more advanced pregnancy may require a hysterectomy to control bleeding. The more advanced the pregnancy the higher the risk for a major bleeding necessitating a hysterectomy.
On a very rare occasion, a cervical pregnancy results in the birth of a live baby, typically the pregnancy is in the upper part of the cervical canal and manages to extend into the lower part of the uterine cavity.
A cervical pregnancy can develop together with a normal intrauterine pregnancy; such a heterotopic pregnancy will call for expert management as to not to endanger the intrauterine pregnancy.
Principles of management are to treat the shock and replace the uterus. The patient should be moved rapidly to the OR to facilitate anesthesia monitoring during this procedure. Usually this complication is only recognized after delivery of the placenta, wherein pitocin has already been started, which just exacerbates the problem. The uterus clamps down around the inversion making it very difficult to perform a replacement. This is a true obstetrical emergency, so extra doctors, nurses, anesthesiologists should be summoned to the room to assist. The pitocin should be turned off immediately. Giving tocolytics such as terbutaline or magnesium sulfate have a lower success rate. Halothane and Nitroglycerine (100mcg to 200 mcg intravenously) have a higher success rate.
Once you have achieved uterine relaxation, place your fist into the vagina. Find the biggest part of the inversion and push with your fist cephalward to replace the uterus. This takes firm steady force, so keep your fist in the vagina if you need to rest your hand. Then continue more force toward the fundus to replace the uterus. You can use your left hand on the outside of the abdomen to help you feel where the fundus should be replaced. This helps guide the angle of your fist in replacing the uterus. Once it is replaced, give the patient Misoprostol 1000 mcgs rectally to help with increasing uterine tone. Other medications such as Methergine and Hemabate can be used. If you have heavy bleeding, consider inserting a Bakri balloon into the uterine cavity to tamponade the bleeding.
These patients have usually sustained heavy blood loss, and should be monitored in the ICU postoperatively. If you have given nitroglycerine, they must have cardiac monitoring postoperatively.
Other personnel should be monitoring vital signs, ordering blood products, assisting the anesthesiologist, drawing labs, and stabilizing the patient. Remember that nitroglycerine can cause hypotension, which can be reversed with ephedrine.
If external replacement fails, a laparotomy may be required, in which the uterus is gently pulled the right way round using forceps.
Advanced abdominal pregnancy refers to situations where the pregnancy continues past 20 weeks of gestation (versus early abdominal pregnancy < 20 weeks). In those situations, live births have been reported in academic journals and also in the lay press where the babies are not uncommonly referred to as 'Miracle babies'. A patient may carry a dead fetus but will not go into labor. Over time, the fetus calcifies and becomes a lithopedion.
It is generally recommended to perform a laparotomy when the diagnosis of an abdominal pregnancy is made. However, if the baby is alive and medical support systems are in place, careful watching could be considered to bring the baby to viability. Women with an abdominal pregnancy will not go into labor. Delivery in a case of an advanced abdominal pregnancy will have to be via laparotomy. The survival of the baby is reduced and high perinatal mortality rates between 40–95% have been reported.
Babies of abdominal pregnancies are prone to birth defects due to compression in the absence of the uterine wall and the often reduced amount of amniotic fluid surrounding the unborn baby. The rate of malformations and deformations is estimated to be about 21%; typical deformations are facial and cranial asymmetries and joint abnormalities and the most common malformations are limb defects and central nervous malformations.
Once the baby has been delivered placental management becomes an issue. In normal deliveries the contraction of uterus provides a powerful mechanism to control blood loss, however, in an abdominal pregnancy the placenta is located over tissue that cannot contract and attempts of its removal may lead to life-threatening blood loss. Thus blood transfusion is frequent in the management of patients with this kind of pregnancy, with others even using tranexamic acid and recombinant factor VIIa, which both minimize blood loss.
Generally, unless the placenta can be easily tied off or removed, it may be preferable to leave it in place and allow for a natural regression. This process may take several months and can be monitored by clinical examination, checking human chorionic gonadotropin levels and by ultrasound scanning (in particular using doppler ultrasonography. Use of methotrexate to accelerate placental regression is controversial as the large amount of necrotic tissue is a potential site for infection, mifepristone has also be used to promote placental regression. Placental vessels have also been blocked by angiographic embolization. Complications of leaving the placenta can include residual bleeding, infection, bowel obstruction, pre-eclampsia (which may all necessitate further surgery) and failure to breast feed due to placental hormones.
Outcome with abdominal pregnancy can be good for the baby and mother, Lampe described an abdominal pregnancy baby and her mother who were well more than 22 years after surgery.