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Most women with a PUL are followed up with serum hCG measurements and repeat TVS examinations until a final diagnosis is confirmed. Low-risk cases of PUL that appear to be failing pregnancies may be followed up with a urinary pregnancy test after 2 weeks and get subsequent telephone advice. Low-risk cases of PUL that are likely intrauterine pregnancies may have another TVS in 2 weeks to access viability. High-risk cases of PUL require further assessment, either with a TVS within 48 h or additional hCG measurement.
A laparoscopy or laparotomy can also be performed to visually confirm an ectopic pregnancy. This is generally reserved for women presenting with signs of an acute abdomen and/or hypovolemic shock. Often if a tubal abortion or tubal rupture has occurred, it is difficult to find the pregnancy tissue. A laparoscopy in very early ectopic pregnancy rarely shows a normal looking fallopian tube.
Culdocentesis, in which fluid is retrieved from the space separating the vagina and rectum, is a less commonly performed test that may be used to look for internal bleeding. In this test, a needle is inserted into the space at the very top of the vagina, behind the uterus and in front of the rectum. Any blood or fluid found may have been derived from a ruptured ectopic pregnancy.
Progesterone levels of less than 20 nmol/l have a high predictive value for failing pregnancies, whilst levels over 25 nmol/l are likely to predict viable pregnancies, and levels over 60 nmol/l are strongly so. This may help in identifying failing PULs that are at low risk and thereby needing less follow-up. Inhibin A may also be useful for predicting spontaneous resolution of PUL, but is not as good as progesterone for this purpose.
In addition, there are various mathematical models, such as logistic regression models and Bayesian networks, for the prediction of PUL outcome based on multiple parameters. Mathematical models also aim to identify PULs that are "low risk", that is, failing PULs and IUPs.
Dilation and curettage is sometimes used to diagnose pregnancy location with the aim of differentiating between an EP and a non-viable IUP in situations where a viable IUP can be ruled out. Specific indications for this procedure include either of the following:
- no visible IUP on transvaginal ultrasonography with a serum hCG of more than 2000 IU/ml
- an abnormal rise in hCG level. A rise of 35% over 48 hours is proposed as the minimal rise consistent with a viable intrauterine pregnancy.
- an abnormal fall in hCG level, such as defined as one of less than 20% in 2 days
Depending on gestational age the differential diagnoses for abdominal pregnancy include miscarriage, intrauterine fetal death, placental abruption, an acute abdomen with an intrauterine pregnancy and a fibroid uterus with an intrauterine pregnancy .
To diagnose the rare primary abdominal pregnancy, Studdiford's criteria need to be fulfilled: tubes and ovaries should be normal, there is no abnormal connection (fistula) between the uterus and the abdominal cavity, and the pregnancy is related solely to the peritoneal surface without signs that there was a tubal pregnancy first. Studdiford's criteria were refined in 1968 by Friedrich and Rankin to include microscopic findings.
A possible pregnancy must be considered in any woman who has abdominal pain or abnormal vaginal bleeding. A heterotopic pregnancy may have similar signs and symptoms as a normal intrauterine pregnancy, a normal intrauterine pregnancy and a ruptured ovarian cyst, a corpus luteum, or appendicitis. Blood tests and ultrasound can be used to differentiate these conditions.
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.
Transvaginal ultrasonography has become the primary method of assessment of the health of an early pregnancy.
In non-pregnant patients who are evaluated for recurrent pregnancy loss the following tests are usually performed.
Parental chromosome testing (karyogram) is generally recommended after 2 or 3 pregnancy losses. Blood tests for thrombophilia, ovarian function, thyroid function and diabetes are performed.
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.
Extrauterine pregnancies are non-viable and can be fatal to the mother if left untreated. The mortality rate for the extrauterine pregnancy is approximately 35%.
Ovarian pregnancies are dangerous and prone to internal bleeding. Thus, when suspected, intervention is called for.
Traditionally, an explorative laparotomy was performed, and once the ovarian pregnancy was identified, an oophorectomy or salpingo-oophorectomy was performed, including the removal of the pregnancy. Today, the surgery can often be performed via laparoscopy. The extent of surgery varies according to the amount of tissue destruction that has
occurred. Patients with an ovarian pregnancy have a good prognosis for future fertility and therefore conservative surgical management is advocated. Further, in attempts to preserve ovarian tissue, surgery may involve just the removal of the pregnancy with only a part of the ovary. This can be accomplished by an ovarian wedge resection.
Ovarian pregnancies have been successfully treated with methotrexate since it was introduced in the management of ectopic pregnancy in 1988.
An ovarian pregnancy can develop together with a normal intrauterine pregnancy; such a heterotopic pregnancy will call for expert management as not to endanger the intrauterine pregnancy.
Patients with an ectopic pregnancy are generally at higher risk for a recurrence, however, there are no specific data for patients with an interstitial pregnancy. When a new pregnancy is diagnosed it is important to monitor the pregnancy by transvaginal sonography to assure that is it properly located, and that the surgically repaired area remains intact. Cesarean delivery is recommended to avoid uterine rupture during labor.
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.
Amniocentesis and chorionic villus sampling are procedures conducted to assess the fetus. A sample of amniotic fluid is obtained by the insertion of a needle through the abdomen and into the uterus. Chorionic villus sampling is a similar procedure with a sample of tissue removed rather than fluid. These procedures are not associated with pregnancy loss during the second trimester but they are associated with miscarriages and birth defects in the first trimester. Miscarriage caused by invasive prenatal diagnosis (chorionic villus sampling (CVS) and amniocentesis) is rare (about 1%).
Chronic Endometritis (CE) due to common bacteria has been found to be prevalent in some women with a history of recurrent miscarriage. One study found that 71 percent of women who tested positive for this condition were successfully treated by an antibiogram-based antibiotic treatment. 78.4 percent of these women subsequently became pregnant in the year following treatment. The study concludes that "CE is frequent in women with recurrent miscarriages," and that "antibiotic treatment seems to be associated with an improved reproductive outcome." The authors also conclude, "that hysteroscopy should be a part of the diagnostic workup of infertile women complaining of unexplained recurrent miscarriage."
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.
Generally gynecologic hemorrhage does not arise out of nowhere. Regular gynecologic examinations, cancer screening, and contraceptive measures go a long way in preventing and forestalling unsuspected acute bleeding events.
Cases of GTD can be diagnosed through routine tests given during pregnancy, such as blood tests and ultrasound, or through tests done after miscarriage or abortion. Vaginal bleeding, enlarged uterus, pelvic pain or discomfort, and vomiting too much (hyperemesis) are the most common symptoms of GTD. But GTD also leads to elevated serum hCG (human chorionic gonadotropin hormone). Since pregnancy is by far the most common cause of elevated serum hCG, clinicians generally first suspect a pregnancy with a complication. However, in GTD, the beta subunit of hCG (beta hCG) is also always elevated. Therefore, if GTD is clinically suspected, serum beta hCG is also measured.
The initial clinical diagnosis of GTD should be confirmed histologically, which can be done after the evacuation of pregnancy (see «Treatment» below) in women with hydatidiform mole. However, malignant GTD is highly vascular. If malignant GTD is suspected clinically, biopsy is contraindicated, because biopsy may cause life-threatening haemorrhage.
Women with persistent abnormal vaginal bleeding after any pregnancy, and women developing acute respiratory or neurological symptoms after any pregnancy, should also undergo hCG testing, because these may be signs of a hitherto undiagnosed GTD.
A pelvic examination will typically reveal a single vagina and a single cervix. Investigations are usually prompted on the basis of reproductive problems.
Helpful techniques to investigate the uterine structure are transvaginal ultrasonography and sonohysterography, hysterosalpingography, MRI, and hysteroscopy. More recently 3-D ultrasonography has been advocated as an excellent non-invasive method to evaluate uterine malformations.
Women with a hydatidiform mole have an excellent prognosis. Women with a malignant form of GTD usually have a very good prognosis.
Choriocarcinoma, for example, is an uncommon, yet almost always curable cancer. Although choriocarcinoma is a highly malignant tumour and a life-threatening disease, it is very sensitive to chemotherapy. Virtually all women with non-metastatic disease are cured and retain their fertility; the prognosis is also very good for those with metastatic (spreading) cancer, in the early stages, but fertility may be lost. 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. Only a few women with GTD have a poor prognosis, e.g. some forms of stage IV GTN. The FIGO staging system is used. The risk can be estimated by scoring systems such as the "Modified WHO Prognostic Scoring System", wherein scores between 1 and 4 from various parameters are summed together:
In this scoring system, women with a score of 7 or greater are considered at high risk.
It is very important for malignant forms of GTD to be discovered in time. In Western countries, women with molar pregnancies are followed carefully; for instance, in the UK, all women who have had a molar pregnancy are registered at the National Trophoblastic Screening Centre. There are efforts in this direction in the developing countries too, and there have been improvements in these countries in the early detection of choriocarcinoma, thereby significantly reducing the mortality rate also in developing countries.
While a full testing of tubal functions in patients with infertility is not possible, testing of tubal patency is feasible. A hysterosalpingogram will demonstrate that tubes are open when the radioopaque dye spills into the abdominal cavity. Sonography can demonstrate tubal abnormalities such as a hydrosalpinx indicative of tubal occlusion. During surgery, typically laparoscopy, the status of the tubes can be inspected and a dye such as methylene blue can be injected in a process termed chromotubation into the uterus and shown to pass through the tubes when the cervix is occluded. Laparoscopic chromotubation has been described as the gold standard of tubal evaluation. As tubal disease is often related to Chlamydia infection, testing for Chlamydia antibodies has become a cost-effective screening device for tubal pathology.
Tubal insufflation is only of historical interest as an older office method to indicate patency; it was used prior to laparoscopic evaluation of pelvic organs.
A review article in The New England Journal of Medicine based on a consensus meeting of the Society of Radiologists in Ultrasound in America (SRU) has suggested that miscarriage should be diagnosed only if any of the following criteria are met upon ultrasonography visualization:
A unicornuate uterus may be associated with a rudimentary horn on the opposite site. This horn may be communicating with the uterus, and linked to the ispilateral tube. Occasionally a pregnancy may implant into such a horn setting up a dangerous situation as such pregnancy can lead to a potentially fatal uterine rupture. Surgical resection of the horn is indicated.
A history will establish if the condition is acute or chronic, and if external circumstances are involved. A gynecologic examination is usually complemented by a gynecologic ultrasonography. A blood count determines the degree of anemia and may point out bleeding problems. The pregnancy test is important, particularly as bleeding in early pregnancy presents as gynecological hemorrhage and ectopic pregnancy can be fatal.
Diagnosis is broadly classified into supportive and definitive investigations:
Hydrosalpinx may be diagnosed using ultrasonography as the fluid filled elongated and distended tubes display their typical echolucent pattern. However, a small hydrosalpinx may be missed by sonography. During an infertility work-up a hysterosalpingogram (HSG), an X-ray procedure that uses a contrast agent to image the fallopian tubes, shows the retort-like shape of the distended tubes and the absence of spillage of the dye into the peritoneum. If, however, there is a tubal occlusion at the utero-tubal junction, a hydrosalpinx may go undetected. When a hydrosalpinx is detected by an HSG it is prudent to administer antibiotics to reduce the risk of reactivation of an inflammatory process.
When laparoscopy is performed, the surgeon may note the distended tubes, identify the occlusion, and may also find associated adhesions affecting the pelvic organs. Laparoscopy not only allows for the diagnosis of hydrosalpinx, but also presents a platform for intervention (see management).
Obstetric ultrasonography can detect fetal abnormalities, detect multiple pregnancies, and improve gestational dating at 24 weeks. The resultant estimated gestational age and due date of the fetus are slightly more accurate than methods based on last menstrual period. Ultrasound is used to measure the nuchal fold in order to screen for Downs syndrome.