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Molar pregnancies usually present with painless vaginal bleeding in the fourth to fifth month of pregnancy. The uterus may be larger than expected, or the ovaries may be enlarged. There may also be more vomiting than would be expected (hyperemesis). Sometimes there is an increase in blood pressure along with protein in the urine. Blood tests will show very high levels of human chorionic gonadotropin (hCG).
Molar pregnancy is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus and will fail to come to term.
A molar pregnancy is a gestational trophoblastic disease which grows into a mass in the uterus that has swollen chorionic villi. These villi grow in clusters that resemble grapes. A molar pregnancy can develop when a fertilized egg does not contain an original maternal nucleus. The products of conception may or may not contain fetal tissue. It is characterized by the presence of a hydatidiform mole (or hydatid mole, mola hydatidosa). Molar pregnancies are categorized as partial moles or complete moles, with the word "mole" being used to denote simply a clump of growing tissue, or a "growth".
A complete mole is caused by a single sperm (incidence is about 90%) or two (incidence is about 10%) sperms combining with an egg which has lost its DNA (in the first case the sperm then reduplicates forming a "complete" 46 chromosome set). The genotype is typically 46,XX (diploid) due to subsequent mitosis of the fertilizing sperm, but can also be 46,XY (diploid). 46,YY (diploid) is not observed. In contrast, a partial mole occurs when a haploid egg is fertilized by two sperm or by one sperm which reduplicates itself yielding the genotypes of 69,XXY (triploid) or 92,XXXY (tetraploid). Complete hydatidiform moles have 2 - 4% risk of developing into choriocarcinoma in Western countries and 10 - 15% in Eastern countries and overall, also a 15% chance of becoming an invasive mole. Incomplete moles can become invasive (<5% risk) but are not associated with choriocarcinoma. Complete hydatidiform moles account for 50% of all cases of choriocarcinoma.
Invasive hydatidiform mole, also known as invasive mole and chorioadenoma destruens is a type of neoplasia that grows into the muscular wall of the uterus. It is formed after conception (fertilization of an egg by a sperm). It may spread to other parts of the body, such as the vagina, vulva, and lung.
Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumours. These tumours are rare, and they appear when cells in the womb start to proliferate uncontrollably. The cells that form gestational trophoblastic tumours are called trophoblasts and come from tissue that grows to form the placenta during pregnancy.
There are several different types of GTD. Hydatidiform moles are benign in most cases, but sometimes may develop into invasive moles, or, in rare cases, into choriocarcinoma, which is likely to spread quickly, but which is very sensitive to chemotherapy, and has a very good prognosis. Gestational trophoblasts are of particular interest to cell biologists because, like cancer, these cells invade tissue (the uterus), but unlike cancer, they sometimes "know" when to stop.
GTD can simulate pregnancy, because the uterus may contain fetal tissue, albeit abnormal. This tissue may grow at the same rate as a normal pregnancy, and produces chorionic gonadotropin, a hormone which is measured to monitor fetal well-being.
While GTD overwhelmingly affects women of child-bearing age, it may rarely occur in postmenopausal women.
Up to 10% of women with ectopic pregnancy have no symptoms, and one-third have no medical signs. In many cases the symptoms have low specificity, and can be similar to those of other genitourinary and gastrointestinal disorders, such as appendicitis, salpingitis, rupture of a corpus luteum cyst, miscarriage, ovarian torsion or urinary tract infection. Clinical presentation of ectopic pregnancy occurs at a mean of 7.2 weeks after the last normal menstrual period, with a range of 4 to 8 weeks. Later presentations are more common in communities deprived of modern diagnostic ability.
Signs and symptoms of ectopic pregnancy include increased hCG, vaginal bleeding (in varying amounts), sudden lower abdominal pain, pelvic pain, a tender cervix, an adnexal mass, or adnexal tenderness. In the absence of ultrasound or hCG assessment, heavy vaginal bleeding may lead to a misdiagnosis of miscarriage. Nausea, vomiting and diarrhea are more rare symptoms of ectopic pregnancy.
Rupture of an ectopic pregnancy can lead to symptoms such as abdominal distension, tenderness, peritonism and hypovolemic shock. A woman with ectopic pregnancy may be excessively mobile with upright posturing, in order to decrease intrapelvic blood flow, which can lead to swelling of the abdominal cavity and cause additional pain.
Gestational trophoblastic disease (GTD) may also be called gestational trophoblastic tumour (GTT).
Hydatidiform mole (one type of GTD) may also be called molar pregnancy.
Persistent disease; persistent GTD: If there is any evidence of persistence of GTD, usually defined as persistent elevation of beta hCG (see «Diagnosis» below), the condition may also be referred to as gestational trophoblastic neoplasia (GTN).
An interstitial pregnancy is a uterine but ectopic pregnancy; the pregnancy is located outside the uterine cavity in that part of the fallopian tube that penetrates the muscular layer of the uterus. The term cornual pregnancy is sometimes used as a synonym, but remains ambiguous as it is also applied to indicate the presence of a pregnancy located within the cavity in one of the two upper "horns" of a bicornuate uterus. Interstitial pregnancies have a higher mortality than ectopics in general.
Ovarian pregnancy refers to an ectopic pregnancy that is located in the ovary. Typically the egg cell is not released or picked up at ovulation, but fertilized within the ovary where the pregnancy implants. Such a pregnancy usually does not proceed past the first four weeks of pregnancy. An untreated ovarian pregnancy causes potentially fatal intraabdominal bleeding and thus may become a medical emergency.
A Cervical pregnancy is an ectopic pregnancy that has implanted in the uterine endocervix. Such a pregnancy typically aborts within the first trimester, however, if it is implanted closer to the uterine cavity - a so-called cervico-isthmic pregnancy - it may continue longer. Placental removal in a cervical pregnancy may result in major hemorrhage.
Trophoblastic neoplasms derive from trophoblastic tissue. Examples include:
- Choriocarcinoma
- Hydatidiform mole
A placental disease is any disease, disorder, or pathology of the placenta. The article also covers placentation abnormalities, which is often used synonymously for placental disease.
Ectopic pregnancy, also known as tubal pregnancy, is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding. Less than 50 percent of affected women have both of these symptoms. The pain may be described as sharp, dull, or crampy. Pain may also spread to the shoulder if bleeding into the abdomen has occurred. Severe bleeding may result in a fast heart rate, fainting, or shock. With very rare exceptions the fetus is unable to survive.
Risk factors for ectopic pregnancy include: pelvic inflammatory disease, often due to Chlamydia infection, tobacco smoking, prior tubal surgery, a history of infertility, and the use of assisted reproductive technology. Those who have previously had an ectopic pregnancy are at much higher risk of having another one. Most ectopic pregnancies (90%) occur in the Fallopian tube which are known as tubal pregnancies. Implantation can also occur on the cervix, ovaries, or within the abdomen. Detection of ectopic pregnancy is typically by blood tests for human chorionic gonadotropin (hCG) and ultrasound. This may require testing on more than one occasion. Ultrasound works best when performed from within the vagina. Other causes of similar symptoms include: miscarriage, ovarian torsion, and acute appendicitis.
Prevention is by decreasing risk factors such as chlamydia infections through screening and treatment. While some ectopic pregnancies will resolve without treatment, this approach has not been well studied as of 2014. The use of the medication methotrexate works as well as surgery in some cases. Specifically it works well when the beta-HCG is low and the size of the ectopic is small. Surgery is still typically recommended if the tube has ruptured, there is a fetal heartbeat, or the person's vital signs are unstable. The surgery may be laparoscopic or through a larger incision, known as a laparotomy. Outcomes are generally good with treatment.
The rate of ectopic pregnancy is about 1 and 2% that of live births in developed countries, though it may be as high as 4% among those using assisted reproductive technology. It is the most common cause of death among women during the first trimester at approximately 10% of the total. In the developed world outcomes have improved while in the developing world they often remain poor. The risk of death among those in the developed world is between 0.1 and 0.3 percent while in the developing world it is between one and three percent. The first known description of an ectopic pregnancy is by Al-Zahrawi in the 11th century. The word "ectopic" means "out of place".
The diagnosis is made in asymptomatic pregnant women either by inspection seeing a bluish discolored cervix or, more commonly, by obstetric ultrasonography. A typical non-specific symptom is vaginal bleeding during pregnancy. Ultrasound will show the location of the gestational sac in the cervix, while the uterine cavity is "empty". Cervical pregnancy can be confused with a miscarriage when pregnancy tissue is passing through the cervix.
Histologically the diagnosis has been made by Rubin’s criteria on the surgical specimen: cervical glands are opposite the trophoblastic tissue, the trophoblastic attachment is below the entrance of the uterine vessels to the uterus or the anterior peritoneal reflection, and fetal elements are absent from the uterine corpus. As many pregnancies today are diagnosed early and no hysterectomy is performed, Rubin's criteria can often not be applied.
Chorionic hematoma (also chorionic hemorrhage) is the pooling of blood (hematoma) between the chorion, a membrane surrounding the embryo, and the uterine wall. It occurs in about 3.1% of all pregnancies, it is the most common sonographic abnormality and the most common cause of first trimester bleeding.
Placenta accreta occurs when all or part of the placenta attaches abnormally to the myometrium (the muscular layer of the uterine wall). Three grades of abnormal placental attachment are defined according to the depth of attachment and invasion into the muscular layers of the uterus:
- Accreta – chorionic villi attach to the myometrium, rather than being restricted within the decidua basalis.
- Increta – chorionic villi invade into the myometrium.
- Percreta – chorionic villi invade through the perimetrium (uterine serosa).
Because of abnormal attachment to the myometrium, placenta accreta is associated with an increased risk of heavy bleeding at the time of attempted vaginal delivery. The need for transfusion of blood products is frequent, and hysterectomy is sometimes required to control life-threatening hemorrhage.
The diagnosis is made in asymptomatic pregnant women by obstetric ultrasonography. On pelvic examination a unilateral adnexal mass may be found. Typical symptoms are abdominal pain and, to a lesser degree, vaginal bleeding during pregnancy. Patients may present with hypovolemia or be in circulatory shock because of internal bleeding.
Ideally, ultrasound will show the location of the gestational sac in the ovary, while the uterine cavity is "empty", and if there is internal bleeding, it can be identified. Because of the proximity of the tube, the sonographic distinction between a tubal and an ovarian pregnancy may be difficult. Serial hCG levels generally show not the normal progressive rise.
In a series of 12 patients the mean gestation age was 45 days.
Histologically, the diagnosis has been made by Spiegelberg criteria on the surgical specimen of the removed ovary and tube. However, the tube and ovary are not usually removed as sonography allows for earlier diagnosis and surgeons strive to preserve the ovary. Prior to the introduction of Spiegelberg's criteria in 1878, the existence of ovarian pregnancy was in doubt; his criteria helped to identify the ovarian pregnancy from other ectopics:
- The gestational sac is located in the region of the ovary.
- The gestational sac is attached to the uterus by the ovarian ligament.
- Ovarian tissue is histologically proven in the wall of the gestational sac.
- The oviduct on the affected side is intact (this criterion, however, holds not true for a longer ongoing ovarian pregnancy).
An ovarian pregnancy can be mistaken for a tubal pregnancy or a hemorrhagic ovarian cyst or corpus luteum prior to surgery. Sometimes, only the presence of trophoblastic tissue during the histologic examination of material of a bleeding ovarian cyst shows that an ovarian pregnancy was the cause of the bleeding.
Chorionic hematomas can be caused by the separation of the chorion from the endometrium (inner membrane of the uterus). Hematomas are classified by their location between tissue layers:
- Subchorionic hematomas, the most common type, are between the chorion and endometrium.
- Retroplacental hematomas are entirely behind the placenta and not touching the gestational sac.
- Subamniotic or preplacental hematomas are contained within amnion and chorion. Rare.
Most patients with a small subchorionic hematoma are asymptomatic. Symptoms include vaginal bleeding, abdominal pain, premature labor and threatened abortion.
Ultrasonography is the preferred method of diagnosis. A chorionic hematoma appears on ultrasound as a hypoechoic crescent adjacent to the gestational sac. The hematoma is considered small if it is under 20% of the size of the sac and large if it is over 50%.
When the antepartum diagnosis of placenta accreta is made, it is usually based on ultrasound findings in the second or third trimester. Sonographic findings that may be suggestive of placenta accreta include:
1. Loss of normal hypoechoic retroplacental zone
2. Multiple vascular lacunae (irregular vascular spaces) within placenta, giving "Swiss cheese" appearance
3. Blood vessels or placental tissue bridging uterine-placental margin, myometrial-bladder interface, or crossing the uterine serosa
4. Retroplacental myometrial thickness of <1 mm
5. Numerous coherent vessels visualized with 3-dimensional power Doppler in basal view
Although there are isolated case reports of placenta accreta being diagnosed in the first trimester or at the time of abortion <20 weeks' gestational age, the predictive value of first-trimester ultrasound for this diagnosis remains unknown. Women with a placenta previa or "low-lying placenta" overlying a uterine scar early in pregnancy should undergo follow-up imaging in the third trimester with attention to the potential presence of placenta accreta.
Early diagnosis is important and today facilitated by the use of sonography and the quantitative human chorionic gonadotropin (hCG) assay. As in other cases of ectopic pregnancy, risk factors are: previous tubal pregnancy, IVF therapy, tubal surgery, and a history of sexual infection.
Typical symptoms of an interstitial pregnancy are the classic signs of ectopic pregnancy, namely abdominal pain and vaginal bleeding. Hemorrhagic shock is found in almost a quarter of patients.; this explains the relatively high mortality rate.
In pregnant patients, sonography is the primary method to make the diagnosis, even when patients have no symptoms. The paucity of myometrium around the gestational sac is diagnostic, while, in contrast, the angular pregnancy has at least 5 mm of myometrium on all of its sides. Ultrasonic criteria for the diagnosis include an empty uterine cavity, a gestational sac separate from the uterine cavity, and a myometrial thinning of less than 5 mm around the gestational sac; typically the "interstitial line sign"—an echogenic line from the endometrial cavity to the corner next to the gestational mass—is seen. MRI can be used particularly when it is important to distinguish between an interstitial and angular pregnancy.
On average, the gestational age at presentation is about 7–8 weeks. In a 2007 series, 22% of patients presented with rupture and hemorrhagic shock, while a third of the patients were asymptomatic; the remainder had abdominal pain and/or vaginal bleeding. Cases that are not diagnosed until surgery show an asymmetrical bulge in the upper corner of the uterus.
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.
Some or all of the following symptoms may be present, though it is possible not to experience any symptoms:
- Abdominal pain. Dull aching pain within the abdomen or pelvis, especially during intercourse.
- Uterine bleeding. Pain during or shortly after beginning or end of menstrual period; irregular periods, or abnormal uterine bleeding or spotting.
- Fullness, heaviness, pressure, swelling, or bloating in the abdomen.
- When a cyst ruptures from the ovary, there may be sudden and sharp pain in the lower abdomen on one side.
- Change in frequency or ease of urination (such as inability to fully empty the bladder), or difficulty with bowel movements due to pressure on adjacent pelvic anatomy.
- Constitutional symptoms such as fatigue, headaches
- Nausea or vomiting
- Weight gain
Other symptoms may depend on the cause of the cysts:
- Symptoms that may occur if the cause of the cysts is polycystic ovarian syndrome (PCOS) may include increased facial hair or body hair, acne, obesity and infertility.
- If the cause is endometriosis, then periods may be heavy, and intercourse painful.
The effect of cysts not related to PCOS on fertility is unclear.
A ruptured ovarian cyst is usually self-limiting, and only requires keeping an eye on the situation and pain medications. The main symptom is abdominal pain, which may last a few days to a several weeks, but they can also be asymptomatic. Rupture of large ovarian cysts can cause bleeding inside the abdominal cavity and in some cases shock.
The symptoms and discomforts of pregnancy are those presentations and conditions that result from pregnancy but do not significantly interfere with activities of daily living or pose a threat to the health of the mother or baby. This is in contrast to pregnancy complications. Sometimes a symptom that is considered a discomfort can be considered a complication when it is more severe. For example, nausea (morning sickness) can be a discomfort, but if, in combination with significant vomiting it causes a water-electrolyte imbalance, it is a complication known as hyperemesis gravidarum.
Common symptoms and discomforts of pregnancy include:
- Tiredness.
- Constipation
- Pelvic girdle pain
- Back pain
- Braxton Hicks contractions. Occasional, irregular, and often painless contractions that occur several times per day.
- Edema (swelling). Common complaint in advancing pregnancy. Caused by compression of the inferior vena cava and pelvic veins by the uterus leads to increased hydrostatic pressure in lower extremities.
- Increased urinary frequency. A common complaint, caused by increased intravascular volume, elevated glomerular filtration rate, and compression of the bladder by the expanding uterus.
- Urinary tract infection
- Varicose veins. Common complaint caused by relaxation of the venous smooth muscle and increased intravascular pressure.
- Haemorrhoids (piles). Swollen veins at or inside the anal area. Caused by impaired venous return, straining associated with constipation, or increased intra-abdominal pressure in later pregnancy.
- Regurgitation, heartburn, and nausea.
- Stretch marks
- Breast tenderness is common during the first trimester, and is more common in women who are pregnant at a young age.
In addition, pregnancy may result in pregnancy complication such as deep vein thrombosis or worsening of an intercurrent disease in pregnancy.
Theca lutein cyst is a type of bilateral functional ovarian cyst filled with clear, straw-colored fluid. To be classified a functional cyst, the mass must reach a diameter of at least three centimeters.
These cysts result from exaggerated physiological stimulation (hyperreactio luteinalis) and are usually associated with markedly elevated levels of beta-human chorionic gonadotropin (beta-hCG). They are thus associated with gestational trophoblastic disease (molar pregnancy), diabetes mellitus, alloimmunisation to Rh-D, and multiple gestations. They have rarely been associated with chronic kidney disease (secondary to reduced hCG clearance) and hyperthyroidism (given the structural homology with TSH). These cysts resolve after pregnancy. Rarely, when the theca-lutein cysts are stimulated by gonadotropins, massive ascites can result. In most cases however, abdominal symptoms are minimal and restricted to peritoneal irritation from cyst hemorrhage. Surgical intervention may be required to remove ruptured or infarcted tissue.
Women who smoke have a twofold increase for functional cysts.
In ICD-10, early pregnancy bleeding (code O20.9) refers to obstetrical hemorrhage before 20 completed weeks of gestational age.
First trimester bleeding, is obstetrical hemorrhage in the first trimester (0 weeks-12 weeks of gestational age). First trimester bleeding is a common occurrence and estimated to occur in approximately 25% of all (clinically recognized) pregnancies.
Differential diagnosis of first trimester bleeding is as follows, with the mnemonic AGE IS Low (during first trimester):
- Abortion (spontaneous), also referred to as miscarriage. One study came to the result that the risk of miscarriage during the course of the pregnancy with just spotting during the first trimester was 9%, and with light bleeding 12%, compared to 12% in pregnancies without any first trimester bleeding. However, heavy first trimester bleeding was estimated to have a miscarriage risk of 24%.
- Gestational trophoblastic neoplasia
- Ectopic pregnancy, which implies a pregnancy outside the uterus, commonly in the fallopian tube, which may lead to bleeding internally that could be fatal if untreated. In cases where there is heavy bleeding and an obstetric ultrasonography assists in diagnosing a pregnancy of unknown location (no visible intrauterine pregnancy), it has been estimated that approximately 6% have an underlying ectopic pregnancy.
- Implantation bleeding
- Chorionic hematoma
- Spotting
- Lower GU tract causes
- Vaginal bleed
- Cervical bleed
Other causes of early pregnancy bleeding may include:
- Postcoital bleeding, which is vaginal bleeding after sexual intercourse that can be normal with pregnancy
- Iatrogenic causes, or bleeding due to medical treatment or intervention, such as sex steroids, anticoagulants, or intrauterine contraceptive devices
- Infection