4/14 D/O of implantation Flashcards
What are trophoblasts?
Trophoblasts - cells forming the outer layer of a blastocyst, which provide nutrients to the embryo and develop into a large part of the placenta
Briefly describe the fetal:maternal circulation at the level of the placenta
- fetal venous blood is circulated back to mom via two umbilical arteries (remember they branch off the internal iliacs)
- fresh maternal blood goes to back to the fetus via a single umbilical vein (remember it connects to the IVC in the fetus)
- maternal blood comes in through the spiral arteries and bathes the terminal villi; exchange of nutrients, gases, etc occurs at the surface of the villous membrane
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T/F fetal/maternal blood mixes at the level of the placenta.
FALSE. fetal/maternal blood does not mix!
What are the placental villi lined by?
syncytiotrophoblast
(remember these cells also produce hCG and
estriol)
What are the d/o of early pregnancy?
- SPONTANEOUS abortion
- ECTOPIC pregnancy
- ABNORMAL IMPLANTATION
- Hypertensive Disorders
- Gestational Trophoblastic Disease (GTD)
fetal causes of spontaneous abortion? maternal causes?
Fetal causes
- defective implantation
- genetic causes (aneuploidy, polyploidy, translocation accounts for 50% of early abortions)
Maternal causes
- inflammatory or infectious diseases (toxoplasma, mycoplasma, listeria, viruses)
- uterine abnormalities
- leiomyoma (fibroid, muscular growth in the wall of the uterus)
- polyps (glandular growth in the endometrium)
- anatomical defects
- Hormonal/metabolic abnormalities
What are the types of spontaneous abortions?
- complete - spontaneous expulsion of all fetal and placental tissue from the uterine cavity
- incomplete - passage of some but not all fetal or placental tissue through the cervix; have to surgically retrieve remaining tissue (D&C)
- threatened - uterine bleeding from a gestation without cervical dilation or effacement
- inevitable - uterine bleeding from a gestation with cervical dilation but without expulsion of any placental or fetal tissue through the cervix; cannot progress to a normal pregnancy
- missed - fetal death without expulsion of any fetal or maternal tissue for at least 8 weeks; have to surgically intervene via D&C
- septic - any type of abortion that is accompanied by uterine infection
difference between complete + incomplete abortion?
- complete - spontaneous expulsion of all fetal and placental tissue from the uterine cavity
- incomplete - passage of some but not all fetal or placental tissue through the cervix; have to surgically retrieve remaining tissue (D&C)
difference between threatened and inevitable spontaneous abortion?
- threatened - uterine bleeding from a gestation without cervical dilation or effacement
- inevitable - uterine bleeding from a gestation with cervical dilation but without expulsion of any placental or fetal tissue through the cervix; cannot progress to a normal pregnancy
why is a missed spontaneous abortion so disgusting?
fetal death without expulsion of any fetal or maternal tissue for at least 8 weeks; have to surgically intervene via D&C
definition of ectopic fallopian tube?
where does it commonly occur in naturally conceived births? IVF?
Implantation of the fetus in any site other than the normal uterine location (ie tubes, ovaries, omentum, cervix)
naturally conceived births: ampullary + tubal
IVF: heterotopic implantation (ampullary + tubal)
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What is the greatest predisposing factor to ectopic pregnancy?
What other factors can cause it?
pelvic inflammatory disease with chronic salpingitis = greatest predisposing condition because it causes scarring
Other abdominal inflammatory processes = predisposing factors that also cause peritubal adhesions
- appendicitis
- abdominal inflammatory processes endometriosis
- failed tubal ligation
- previous abdominal / pelvic surgery
- assisted reproductive technologies (ART) - ex: IVF
Clinical presentation of ectopic pregnancy?
- typically occurs in first trimester
- Abdominal pain (none, mild or severe)
- Minimal vaginal bleeding - usually spotting or light bleeding
- **Intraperitoneal bleeding - no exit to outside world; ranges from none to life threatening hemorrhage (into intraperitoneal space)
What doest this patient have?
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ectopic pregnancy - uterus does not surround gestational sac
Diagnostic tests (and findings) to establish ectopic pregnancy?
- US – uterus does not surround gestational sac
- Quantitative B-hCG
- Serum progesterone
- culdocentesis
How is US useful in diagnosing atopic pregnancies?
uterus does not surround gestational sac
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How is Quantitative B-hCG useful in diagnosing atopic pregnancies?
- first detectable: at time of implantation
- typically doubles every two days (if it doesn’t, then the pregnancy is likely not viable)
- single value: helps to interpret US findings:
- ß-hCG >1500 w/ US findings in uterus = pregnant!
- ß-hCG >1500 w/o US findings in uterus = ectopic
- serial values: establish viability pregnancy too early for sonographic detection
How is serum progesterone useful in diagnosing an ectopic pregnancy?
- < 5 ng/ml: not consistent with normal intrauterine pregnancy; suggests ectopic
- > 15 ng/ml most consistent with viable intrauterine pregnancy
How is culdocentesis useful in diagnosing an ectopic pregnancy?
method to determine presence of peritoneal blood using a needle to extract fluid from the peritoneal blood from area behind cervix (pouch of Douglas), if any.
painful; not done anymore
How are ectopic pregnancies managed?
-
Methotrexate - stops the growth of rapidly dividing cells (embryonic, fetal, placenta cells)
- given every other day until hCG blood tests confirm that the pregnancy has ended
- Surgical - excise the ectopic pregnancy from the tube
What are the 3 main d/o of placental implantation?
- Placenta accreta
- Placenta increta
- Placenta percreta
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What is placenta accretia?
placenta adheres to the superficial myometrium, but does not penetrate it, with partial or complete absence of decidua
- placenta usually detaches from the uterine wall relatively easily
- great risk of post-partem bleeding
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What is placenta increta?
placenta invades the myometrium
- not all is removed after birth
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What is placenta percreta?
placenta invades the entire myometrium to the uterine serosa
- greatest risk of placenta attaching to other organs such as the rectum or bladder
- usually happens after C-section, where implantation happens in the C-section scar
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What is the main cause of ante-partum bleeding? post-partem bleeding?
post-partem bleeding = placenta accreta
ante-partum bleeding = placental previa
Hypertensive Disorders of Pregnancy
(see 4/14 lecture for FCs)
Gestational Trophoblastic Disease (GTD)
What is it?
What cell type do they orignate from?
What are the 3 types?
- pregnancy-related tumours
- rare, but appear when cells in the womb start to proliferate uncontrollably
- originate from trophoblasts (form the placenta during pregnancy)
- 3 forms
- Hydatidiform mole (molar pregnancy)
- Choriocarcinoma
- Placental site trophoblastic tumor
T/F Gestational Trophoblastic Disease (GTD) arises spontaneously from trophoblast stem cells in the uterus
False. always arises from a conception
biomarker of GTD?
hCG - produced by trophoblast
Gestational Trophoblastic Disease (GTD) treatment?
- MTX
- Actinomycin D
- EMA-CO
Hydatidiform mole
what is it?
Hydatidiform mole (molar pregnancy) - non-viable fertilized egg implants in the uterus and grows into a mass; usually of paternally imprinted chromsomes; 2 types
- complete hydatidiform mole (2n)
- incomplete hydatidiform mole (3n)
How does a complete hydatidiform mole form?
always 2n with paternal chromosomes (androgenetic mole) fertilizing an enucleate egg. 2 scenarios
- most arise from a single 23X sperm, which then duplicated its own chromosome
- rarely dispermy fertilization results in 46XY or 46XX; incompatible with life
What is this? how do you tell?
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complete hydatidiform mole (2n)
no fetal tissue present, just trophoblastic overgrowth - edematous chorionic villi (cyst-like/grape-like clusters) with diffuse trophoblastic proliferation
How is complete hydatidiform mole diagnosed?
- Plateau of hCG over 3 weeks
- Rise in hCG over 2 weeks
how is complete hydatidiform mole managed?
- Evacuation of molar tissue; follow-up with serial hCG testing weekly until it reaches 0 (makes sure all of the trophoblast is gone)
- Avoid pregnancy x 6 months
- Monthly hcg x 6 months
How does a incomplete hydatidiform mole form?
Triploid, two sets of paternal chromosomes + one maternal set due to dispermy fertilization of normal egg; ex:
- 2 sperm + normal egg
- diploid sperm + normal egg
What does this person have? how do you tell?
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abnormal fetal tissue and trophoblastic overgrowth – edematous villi, but not quite as much diffuse trophoblastic proliferation of placental tissue; can see fetal development
How does complete & incomplete hydatidiform mole compare in terms of its progression to persistent or metastatic GTD?
incomplete: can become persistent or metastatic GTD 4%
complete: can become persistent or metastatic GTD 20% of the time
19 yo woman presents with abnormal vaginal bleeding. LMP 10 weeks ago
Vital signs: BP 110/64; P 136
Physical exam shows uterus enlarged to umbilicus, cervix closed with small amount of blood in vagina
Urine pregnancy test positive; Labs: hCG 435,000miU/mL (very high); Hbg 12.8
Diagnosis?
typical molar case!
What is Choriocarcinoma?
What are the two forms?
malignancy of trophoblasts
2 types
- gestational - malignancy of trophoblasts; characterized by early hematogenous spread to the lungs
- non-gestational - germ cell tumor that may arise in the testis or ovary (gonadal origin)
What is Placental site trophoblastic tumor?
biomarker?
prognosis?
Rare GTD composed of intermediate trophoblast cells only (no syncytio-or cytotrophoblasts)
Biomarker: hPL (hCG is very low)
prognosis:
- Often deeply myoinvasive
- Not sensitive to chemotherapy
- less curable when metastatic