• Implantation of the fertilized ovum outside the endometrial cavity is called ectopic pregnancy. The incidence of ectopic pregnancy is about 1-2%. It constitutes 6% of all maternal deaths.
• The most common cause of maternal deaths in the first trimester is ectopic pregnancy.
Ectopic pregnancy localizations
Tubal pregnancies ----- It is the most common ectopic pregnancy localization
Ampulla (70%) ------The most common site of tubal ectopic pregnancy
Istmus (12%) ------The earliest ruptured tubal ectopic pregnancy
Fimbria ---------------(11%)
Interstitial (cornual) (2-3%) ------- It is the latest ruptured tubal ectopic pregnancy.
Ovarian pregnancies
· Abdominal pregnancies------The most mortal ectopic pregnancy
· Intraligamentary pregnancy ------ All occur secondary
Heterotopic pregnancies ------- It is the ectopic pregnancy with the highest incidence with assisted reproductive techniques.
Cervical pregnancies
Ectopic pregnancy in cesarean scar
· Posthysterectomy; rarest ectopic pregnancy
TUBAL ECTOPIC PREGNANCY
• It is the most common type of ectopic pregnancy. Tubal ectopic pregnancies are seen as ampullary, isthmic, fimbrial and interstitial (cornual) in order of frequency.
etiology
• Disruption of tubal anatomy is the main cause of ectopic pregnancies. There has been an increase in the number of ectopic pregnancies in recent years, the most important reason for this is the increase in the rate of salpingitis, ovulation inductions, IVF applications, increased use of contraceptives, tubal surgery and sterilizations, and earlier and more accurate diagnosis of ectopic pregnancies.
• Most ectopic pregnancies occur in multigravid women.
The risk of ectopic pregnancy increases in salpingitis isthmica nodosa, which is an acquired diverticulum of the tubule.
It increases the risk of ectopic pregnancy in peritubal adhesions that occur after appendicitis or endometriosis.
Congenital tubal anomalies, especially intrauterine DES exposure, also increase the risk of ectopic pregnancy.
All contraceptive methods reduce the incidence of ectopic pregnancy. However, the use of tubal sterilization, intrauterine devices with copper and LNG release, and pills containing pure progesterone increase the risk of ectopic pregnancy when pregnant. Barrier methods and combined oral contraceptives do not have an increased risk and are the contraceptive methods with the lowest risk of ectopic pregnancy. No increased risk has also been demonstrated with depot MPA, emergency contraceptive pills, or implants containing etonorgestrel.
There is no increase in the incidence of chromosomal anomalies in ectopic pregnancies.
Clinic
• Classical triad; pain, vaginal bleeding and delayed menstruation. However, these three may not always be seen together.
• Tubal ectopic pregnancies; They may result in tubal rupture, tubal abortion, or resolution of the product of conception..
• While ectopic pregnancies located in the isthmic region rupture in the early period, ectopic pregnancies located in the ampullary region tend to rupture later. Interstitial ectopic pregnancies rupture at the latest.
The earliest rupture occurs in the isthmic region (6-8 weeks), followed by the ampullary region (8-12 weeks), and the latest in the interstitial region (12-16 weeks).
Diagnostic Methods
Quantitative B-hCG measurement
► In a normal intrauterine pregnancy, while beta-hCG doubles in 48 hours in the first 6th week of pregnancy, this doubling rate slows down and does not become constant after the 6th week. This early doubling time may distinguish ectopic pregnancies from intrauterine pregnancies. If this folding is less than 35% in 48 hours in the early period, it indicates that the pregnancy is not normal (abortion, ex fetus, ectopic pregnancy).
Serum progesterone level
► Its level is lower than normal pregnancies. While progesterone level higher than 25 ng/ml excludes 92.5% ectopic pregnancy; Values below 5 ng/ml are found in only 0.3% of normal pregnancies.
Ultrasonography
► There is double decidual ring appearance in 64-95% of normal intrauterine pregnancies on ultrasonography. In ectopic pregnancies, there is usually a single-layered decidual ring appearance. Rarely, a double decidual ring may appear in ectopic pregnancies.
► The presence of vitelline sac (yolk sac) in the gestational sac is superior to the double decidual ring in excluding ectopic pregnancy.
► However, the most valuable finding in excluding an ectopic pregnancy is fetal cardiac activity in the gestational sac on ultrasonography. In addition, intrauterine centrally located false gestational sac, fluid in Douglas, mass in the adnexal region and adnexal rings (eg tubal ring) are also important ultrasonographic findings in terms of suggesting ectopic pregnancy.
► In the differential diagnosis of a mass in the adnexal area, corpus luteum, endometrioma, hydrosalpinx, ovarian masses (dermoid cyst) or pedunculated myoma should be considered.
► The presence of fetal pole and cardiac activity with adnexal located gestational sac is the most specific finding, but it is the least sensitive finding (10-17%).
► In order to obtain pregnancy findings in ultrasonography, the beta-hCG level must rise above a certain determinant level. They can be seen by transvaginal ultrasonography when the beta-hCG level reaches 1,500-2,000 mIU/mL. If an intrauterine pregnancy cannot be seen at these levels, a lost intrauterine pregnancy or ectopic pregnancy should be considered and serial beta-hCG monitoring should be performed. Descriptive in ectopic pregnancies (3-hCG level is 3510 mIU/mL. If an intrauterine pregnancy cannot be seen above this level, ectopic pregnancy should be accepted and treated.
If the beta-hCG level is below the determining levels and the intrauterine cavity is empty, the following differential diagnoses should be considered:
1. Normal intrauterine pregnancy (but too early to be seen)
2. Abnormal intrauterine pregnancy
3. A complete abortion that has just occurred: beta-hCG drops rapidly and within 48 hours
50% decrease
4. Ectopic pregnancy: beta-hCG level increases or plateaus
5. A woman who is not pregnant
laparoscopy
► In many cases, direct imaging with laparoscopy is a reliable diagnostic method and also provides treatment in the case.
Treatment
Medical Treatment (Methotrexate)
► Methotrexate is a folic acid antagonist that inhibits dihydrofolate reductase and inhibits DNA synthesis. A single dose is used. The success of the treatment is around 90% and a second dose may be needed in 15-20% of cases.
► Factors that increase the success of the treatment; (Low level of 3-hCG, small gestational sac, and absence of fetal cardiac activity. However, the most important factor in failure of treatment (high level of 3-hCG. If beta-hCG > 5000 mIU/mL, failure rate)
It is 15%.
► The most common side effects belong to the gastrointestinal tract; nausea, vomiting, stomatitis and abdominal pain. Other side effects; bone marrow suppression, hemorrhagic enteritis, alopecia, dermatitis, elevated liver enzymes, conjunctivitis, anaphylactic reaction and pneumonitis. However, these side effects are rarely seen in low doses and single applications used in ectopic pregnancies. If the treatment is prolonged, Leucovorin can be used to prevent side effects.
contraindications for methotrexate
1. Ruptured ectopic pregnancy (hemodynamically unstable patients)
2. Breastfeeding
3. Immunodeficient
4. Liver diseases (enzyme elevation)
5. Renal diseases (high serum creatinine)
6. Hematological diseases
7. Methotrexate sensitivity
8. Active pulmonary disease
9. Active peptic ulcer
10. Pregnancy
11. Alcoholism
12. Moderate to severe anemia, leukopenia and thrombocytopenia
Surgical treatment
► Laparoscopy is the first preferred method in the surgical treatment of ectopic pregnancies.
0 Salpingostomy
- If there is a desire to reproduce in the future in a hemodynamically stable and non-ruptured case, it should be preferred (it is the least invasive procedure).
- Factors that increase the risk of persistent trophoblastic tissue (5-20%) after linear salpingostomy:
• Very small pregnancies (duration of amenorrhea < 42 days)
• Serum beta-hCG level higher than 3000 mIU/mL
• Small gestational sac ( < 2 cm)
0 Salpingectomy
- Tubal resection can be used in the treatment of ruptured or non-ruptured ectopic pregnancies.
- To prevent recurrence of ectopic pregnancy, the entire tube should be removed.
If the patient is Rh (-) in all ectopic pregnancies, absolute Rh (D) immunoglobulin should be administered.
ovarian pregnancies
• It is the most common of non-tubal ectopic pregnancies . However, another reference book states that abdominal pregnancy is the most common non-tubal ectopic pregnancy.
• Risk factors are like tubal ectopics. However, in vitro fertilization and IUD use, increases the risk. The cases are often confused with ruptured corpus luteum cyst.
• Ovarian cystectomy and/or ovarian wedge resection is the most commonly preferred surgical method in these cases. Systemic or local (into the sac) methotrexate treatment can also be used.
CERVICAL PREGNANCY
• Although it is a very rare type of ectopic pregnancy, it is important because of the high risk of bleeding. The incidence rises with IVF procedures. Other risk factors are previous cesarean deliveries and previous curettage.
• Clinical findings:
► Painless bleeding (90%) (1/3 massive bleeding)
► The external os may be open; but the internal os is turned off.
► The cervix is enlarged and thinned.
• Treatment:
► First of all, medical treatment is tried. Methotrexate can be administered systemically or locally (into the sac).
In ultrasonography, when pressure is applied to the cervix with the transvaginal probe, the gestational sac does not move in cervical pregnancies (sliding sign is negative}, while the sliding sign is positive in incomplete abortion.
ABDOMINAL PREGNANCY
• They can be primary or secondary (following tubal abortion). Ectopic pregnancies have the highest maternal morbidity and mortality. Pregnancy can reach term. However, fetal mortality is also around 95%. The incidence of congenital anomalies is 20%, and the absence of extremities and CNS anomalies are the most common. The most common deformations are facial and/or cranial asymmetry and joint abnormalities.
• Abdominal pregnancy risk factors; pelvic inflammatory disease, multiparity, endometriosis, assisted reproductive techniques and tubal damage.
• Abdominal pregnancies should be terminated as soon as they are detected. If the fetus dies in the abdomen, calcifies and mummifies after a while, lithopedian; If it turns into a yellowish, oily mass, it is called an adiposen.
• If delivery has taken place in abdominal pregnancies, if the nutrition of the placenta can be determined, it is tied and removed. However, if vascular support cannot be determined, the umbilical cord is tied from the area close to the placenta and left in place to prevent bleeding. In cases where the placenta is left, it is followed by serial beta-hCG and ultrasonography. In these cases, methotrexate treatment is still controversial, as it causes sepsis with precipitated tissue necrosis.
INTERSTITIAL PREGNANCY
• Pregnancies located in the proximal segment of the tubule within the uterine muscular tissue. The risk factors are the same as for tubal pregnancies; however, ipsilateral salpingectomy due to ectopic pregnancy is a specific risk factor.
It constitutes a large percentage of deaths due to ectopic pregnancy (2.5%) due to its difficult diagnosis and high vascular support. Depending on the general condition of the patient, methotrexate can be given or laparoscopic cornuostomy or cornual excision can be performed.
INTRALIGAMENTARY PREGNANCY
• It is rare and is the secondary form of ectopic pregnancies, all of which occur as a result of secondary implantation. They abort from the tuba between the leaves of the ligamentum latum. They have clinical findings as in abdominal pregnancy and are treated like it.
heterotopic pregnancy
• It is the coexistence of extrauterine and intrauterine pregnancies.
• It is the ectopic pregnancy form with the highest incidence as a result of the use of assisted reproductive techniques (increases from 1:30000 pregnancies to 1:100-200 pregnancies).
• Since the hCG increase continues due to intrauterine pregnancy, serial beta-hCG is used in the diagnosis.
measurement is not helpful.
• If the continuation of intrauterine pregnancy is desired, systemic treatments should be avoided and ectopic pregnancy should be treated surgically or with KCI injection into the ectopic gestational sac.
cesarean section scar pregnancy
• It is the implantation of the embryo in the cesarean scar in the uterus. It occurs in 1/2000 of all pregnancies.
• Defined ultrasonographic criteria for cesarean scar pregnancy;
► Empty intrauterine cavity
► Empty cervical canal
► Presence of gestational sac located in the anterior part of the uterine isthmus
► Absence of normal myometrium between bladder and gestational sac
► Negative sliding sign
• Treatment; Curettage, methotrexate (local or systemic) or hysteroscopic intervention can be performed under the guidance of ultrasonography.