Q4 - Gestational Tropho. + Congential Female

What is the primary function of the trophoblast?

• Provides nutrients to developing embryo

• Facilitates embryo implantation

• Contributes to formation of placenta

What structures are derived from the trophoblast?

• Outer layer of blastocyst

• Gives rise to placenta + fetal membranes (chorion + amnion)

What are the different types of gestational trophoblastic disorders?

• Complete + partial hydatidform mole

• Invasive mole

• Choriocarcinoma

• Placental site trophoblastic tumor

What are the pathologic characteristics of a molar pregnancy?

• Type of gestational trophoblastic disease

  • Complete moles = abnormal placental tissue + resembles clusters of grapes with absence of fetus

  • Partial moles = abnormal fetal development

Discuss the incidence of molar pregnancy. Where is the incidence the highest?

• Low (overall)

• Higher in Asia

Discuss the different causes & karyotypes of a complete molar pregnancy?

• Cause = abnormal chromosomal multiplication (overgrowth of trophoblastic tissue)

• Karyotypes = fertilization of an empty egg by a sperm, resulting in a diploid karyotype; 46 XX chromosomes

What have been the classic clinical presentations of a molar pregnancy?

• Vaginal bleeding in 1st trimester

• Elevated hCG levels (>100,000 IU/ml)

• Hyperemesis gravidarum

• Preeclampsia

• Decreased AFP (complete hydatidiform mole.)

What has been the classic sonographic appearance of a molar pregnancy?

• "Snowstorm" pattern

• Moderately echogenic soft tissue mass filling uterine cavity; small cystic spaces representing hydropic chorionic villi

What may occur in the ovaries with a mole? What causes it? How often does it occur?  What complications may occur with it?  What is the sonographic appearance?

• Ovarian theca lutein cysts may occur due to elevated hCG levels

• 10-20% of complete moles; 1 in 1,200 pregnancies

• Ovarian torsion, rupture, bleeding, preeclampsia, and, in rare cases, invasive moles or choriocarcinoma

• Bilateral, multiloculated cystic masses

Why are the classic clinical presentations & sonographic appearance of a molar pregnancy now rarely encountered?

• Uncomplicated preg. presenting 1st trimester vaginal bleeding undergo ultrasound examinainzation

• Molar changes or missed abortion is diagnosed which leads to evacuation of uterus

What are the potential benefits of distinguishing a molar pregnancy from a failed pregnancy?

• Early uterine evacuation; failed pregnancy rather than identification of molar change

• Prevent complications; persistent trophoblastic disease, decrease unnecessary interventions, and provide accurate patient counseling

Discuss the sono appearance of 1^st trimester molar pregnancy and what other conditions it may simulate

• Heterogenous intrauterine mass (“snowstorm” or “cluster of grapes” appear.)

• Echogenic, multicystic villi w/ no identifiable fetus or amniotic sac

• Multiple small cystic spaces in placenta; increases uterine size

• Hypervascular

• Stimulate = incomplete or missed abortion, hemorrhagic decidual reaction, hydropic degeneration of placenta, choriocarcinoma, and “twin molar pregnancy”

What are the complications of molar pregnancy?

• Persistent gestational trophoblastic disease (GTN),

• Choriocarcinoma

• Preeclampsia

• Hyperemesis gravidarum

• Anemia

• Hyperthyroidism

What is the treatment for molar pregnancy?

• Surgical removal of the abnormal tissue from the uterus

• Low-risk patients = single-agent chemotherapy; methotrexate with folinic acid

• High-risk pt. = multidrug chemotherapy, weekly EMA-CO protocols

When should the βHCG return to normal levels?

• Complete molar pregnancy = 8-14 weeks

• Partial molar pregnancy = 6-8 weeks

Discuss the different causes & karyotypes of a partial mole

• Cause = normal egg is fertilized by two sperm, or one sperm duplicates itself, resulting in a triploid embryo with an abnormal placenta

• Karyotype = abnormal; usually triploid, occurs when a normal egg is fertilized by two sperm; 69 XXY chromosomes

What are the placental & fetal sonographic findings of a partial mole?

• Placental findings: defined cystic spaces, enlarged placenta, irregular borders, heterogenous/ “swiss cheese” appearance, and hypervascularity

• Fetal findings: growth restriction, structural anomalies, triploidy features, oligo/polyhydraminos, possible fetal demise

What is a coexistent mole? How can this be differentiated from a partial mole? What are the sonographic findings of a coexistent mole?

• Condition where both a normal fetus and a molar pregnancy exist simultaneously

• Coexisting mole = diploid, normal/viable fetus, two separate placental compartments, normal amniotic fluid, very high levels of hCG, high risk of trophoblastic neoplasia

• Partial mole = triploid, fetus is non-viable, single enlarged/ hydropic placenta, oligohydramnios, elevated hCG (not as high as coexisting), and similar risk as coexisting but lower compared to complete mole

• Aka. Twin pregnancy w/ coexisting molar preg.

In what setting does persistent trophoblastic neoplasia arise? What are the symptoms?

• Rare cancer arising from = abnormal trophoblast cells after pregnancy, after a molar pregnancy (most common), can occur after normal pregnancy, miscarriage, or abortion

• Symptom = abnormal vaginal bleeding, abdominal swelling, coughing, shortness of breath, neurologic deficits, increased hCG levels, and pelvic pain

What is the definition of an invasive mole? What is another name for invasive mole?

• Penetration of molar villi from a CHM or PHM (CHM most common), into myometrium or uterine vasculature

• Cancerous growth that develop in uterus after molar pregnancy, where abnormal cells grow into uterine muscle

• Aka. presistent trophoblastic disease

What is a potentially fatal complication of invasive mole?

• Development of choriocarcinoma; rare but aggressive cancer that spreads to other parts of the body

What is the most important risk factor for choriocarcinoma?

• Can occur after CHM, PHM, normal pregnancy, stillbirth, miscarriage or ectopic pregnancy

  • CHM most common

What percentage of choriocarcinomas are preceded by a mole?

• 2% - 3%

What percentage of moles result in choriocarcinoma?

• 12% - 15%

Briefly discuss the rarest gestational trophoblastic neoplasia

• Placental site trophoblastic tumor (PSTT)

  • Develops in area where placenta attatches to uterus; often appears years after preg.

What are the gray-scale & color & spectral Doppler appearances of PTN?

• Gray-scale = heterogeneous, enlarged uterus, myometrial invasion, retained products of conception

• Color Doppler = increased vascularity

• Spectral Doppler = low resistance index, hypervasuclar, arteriovenous shunting, myometrial flow involvement

What rare condition may mimic PTN on color Doppler sonography?

• Uterine arteriovenous malformation

What other conditions have similar spectral Doppler findings as PTN?

• Uterine arteriovenous malformations

• Retained products of conception, endometrial or cervical cancer, placental site trophoblastic tumor, and choriocarcinoma.

 Discuss the process & the tissues that give rise to the ovaries, fallopian tubes, uterus & vagina.

• Ovaries = gonadal mesoderm

• Fallopian tubes = Müllerian ducts

• Uterus = Müllerian ducts

• Vagina = urogenital sinus

  • Müllerian ducts fuse midline to form uterus + upper vagina.

  • Gonadal ridge develops into ovaries, which produce hormones and eggs

  • Urogenital sinus contributes to lower part of the vagina.

What other organ system often has abnormalities when there are uterine anomalies? Why?

• Renal system

  • B/c close embryological relationship b/t müllerian ducts and kidneys can impact one another

What is the most common congenital anomaly of the female genital tract?

• Imperforated hymen

What condition can this cause?

(Most common congenital anomaly of female genital tract)

• Hydro/hematometrocolpos

• Obstruction

What are other causes of hydro/hematometrocolpos?

• Imperforate hymen, vaginal atresia, Mullerian Duct anomalies, cervical atresia or stenosis, congenital absence of uterus/vagina, PID, and functional obstruction

What other anomalies are associated with these causes?

(Hydro/hematometrocolpos)

• Imperforate hymen

• Transverse vaginal septum 

• Vaginal agenesis (Mullerian agenesis)

What condition results from a remnant of the mesonephric/Wolffian duct?

• Uterine didelphys/agenesis = lead to reproductive issues, including infertility

• Gartner duct cysts in vaginal wall = (rare) mesonephric adenocarcinoma in female genital tract

What 3 basic mechanisms result in congenital uterine anomalies?

• Failure of fusion of the Mullerian ducts

• Failure of resorption of Mullerian Ducts

• Abnormal development of the Mullerian ducts

What are the uterine anomalies associated with each of these mechanisms?

• Failure of fusion of Mullerian Ducts —> uterus didelphys, bicornuate uterus, & septate uterus

• Failure of resorption of Mullerian Ducts —> unicornuate uterus & arcuate uterus

• Abnormal development of the ducts —> agenesis/hypoplasia

How can we distinguish between a duplicated uterus & a septated uterus?

• Duplicated uterus = 2 distinct uterine cavities, 2 cervices, deep indentation/ complete seperation, seperated uterine horns/ V-shaped fundus

• Septate uterus = 1 cavity divided by septum, 1 cervix, mild indentation, single external contour, single endometrial stripe divided by septum, single vagina

 What are conditions that might be mistaken for a duplicated or septated uterus?

• Bicornuate uterus

• Fibroids

• Retroverted uterus

• Arcuate uterus

• Uterine synechiae (Asherman syndrome)

What pregnancy complications are associated with uterine anomalies?

• Miscarriage

• Preterm labor

• Abnormal fetal position

• Increased risk of placental complications

• Fetal malpresentation

• Increase risk for C-Section

What congenital uterine anomaly is associated with diethylstilbestrol?

• Clear cell adenocarcinoma of the vagina

• Hypoplastic T-shaped uterus

• Uterine horns

• Endometrial cavity deformities

What other organ system should be evaluated when a congenital anomaly of the uterus is seen?

• Renal system + urinary tract

What genitourinary abnormality is associated with uterus bicornis bicollis with partial vaginal septum?

• Renal agenesis or dysplasia

• Obstructive hemivagina

• Ipsilateral renal anomaly