Embryology

Question 1

Gubernaculum

Answer 1

Connective tissue that aids in the descent of the gonads by steering them into place in both males and females.

It has developed by ~8 weeks and is only present during the development of the genitourinary systems, after which it atrophies. However, females retain two vestigial reminants: the ovarian ligament and the round ligament of the uterus

Question 2

Anatomy of the upper and lower gubernaculum at 15 weeks in a female fetus

Answer 2

Question 3

Timecourse of embryonic vili development

Answer 3

• They’re always one week behind
  
  • The primary form by week 2
  • The secondary by week 3
  • The tertiary by week 4

Question 4

Chorionic villus structure

Answer 4

Note that the terminal villi are the region of gas and nutrient exchange.

In this diagram, the intervillous space is filled with maternal blood.

Question 5

Four layers of the placental membrane

Answer 5

Question 6

Placental sources of VEGF

Answer 6

• The initial source of VEGF is the cytotropoblast
• Later, the Hofbauer cells and stromal cells take over
  
  • Hofbauer cells are placental macrophages

Question 7

Fibrin-type fibrinoid, matrix-type fibrinoid, and Nitabuch’s layer

Answer 7

• Fibrin-type fibrinoid is a product of maternal clotting which replaces degenerating syncytiotrophoblasts
• Matrix-type fibrinoid is secreted by invasive extravillous extratrophoblastic cells
  
  • Together, they form Nitabuch’s layer, a band of fibrinoid tissue thought to serve the role of preventing excessively-deep implantation. Loss of this layer can lead to abnormal placentation invasion

Question 8

Fate of the two layers of the trophoblast

Answer 8

• Outer layer: The syncytiotrophoblast. After implantation, it is replaced by fibrinoid tissue to form Nitabuch’s layer.
• Inner layer: Cytotrophoblast. Stimulates vasculogenesis in the chorion.

Question 9

Risk factors for abnormal placentation

Answer 9

Question 10

Placenta previa

Answer 10

• Form of abnormal placentation
• Pathogenesis not currently understood
• Risks include previous surgery and previous pregnancy
• Generally speaking, the placenta is in front of the cervical os
• Involves areas of sub-optimal vascularized descidua, promoting movement of trophoblasts to the lower uterine cavity

Question 11

Vasa previa

Answer 11

Sub-group of placenta previa

In vasa previa, fetal blood vessels from the placenta or umbilical cord cover the cervical os

Major risks include velamentous or succenturiate-morphology placenta

Question 12

If placenta previa of any form is detected, ___ is contraindicated due to risk of placental hemorrhage.

Answer 12

If placenta previa of any form is detected, any form of vaginal manipulation (vaginal exam, sexual intercourse, etc) is contraindicated due to risk of placental hemorrhage.

Question 13

In placenta previa, ___ is at risk of bleeding.

In vasa previa, ___ is at risk of bleeding.

Answer 13

In placenta previa, the mother is at risk of bleeding.

In vasa previa, the infant is at risk of bleeding.

Question 14

Placenta accreta

Answer 14

• Anchoring placental villi attach to the myometrium instead of the decidua, resulting in a placenta which adheres to the uterine lining
• Prior cessarian section is the main risk factor
• Down the road, the decidua basalis is absent
• Nitabuch’s layer is often disrupted

Question 15

Placenta accreta, increta, and percreta

Answer 15

• Accreta: Decidua basalis is missing, but the placenta is not infriltrative
• Increta: Placenta infiltrates the myometrium, but does not penetrate the serosa
• Percreta: Placenta penetrates through the myometrium into the serosa

Question 16

Risk factors for placenta accreta

Answer 16

Previous cesarean section

Previous myotomy

Previous dilation and curetage

Question 17

Basic embryology of the GU system

Answer 17

Question 18

The Mullerian ducts give rise to. . .

Answer 18

. . . the fallopian tubes, uterus, and and upper 2/3 of vagina

Question 19

The Wolfian ducts give rise to. . .

Answer 19

. . . the ureters, seminal vesicles, vas deferens, and epididymis

Question 20

How a fetus becomes “male”

Answer 20

Question 21

How a fetus becomes “female”

Answer 21

Question 22

How the Mullerian ducts / Paramesonephric ducts form the uterus

Answer 22

Question 23

Three main types of error in Mullerian anomalies

Answer 23

1. Error in fusion: The ducts do not properly fuse, resulting in a “horned” uterus (bicornuate), a uterus with a dominant side (unicornuate), or two completely separate small uteri (uterine didelphys)
2. Errors in septal resorption: The septum between fused ducts persists, resulting in a septate uterus or an arcuate uterus (indentation where the septum was)
3. Errors in organogenesis: All or part of the Mullerian tract fails to form. Namely causes Mullerian agenesis, where the vagina is absent and uterine development is variable.

Question 24

Transverse vaginal septum

Answer 24

• Results from failed Mullerian fusion or failed vaginal canalization

Question 25

Longitudinal vaginal septum

Answer 25

* Defective lateral fusion or incomplete septal resorpton of the caudal portion of the Mullerian ducts * Often seen with uterine didelphys (double uterus)

Question 26

Disorders of Mullerian duct development have no effect on. . .

Answer 26

. . . **the ovaries** The ovaries are **NOT derived from the Mullerian ducts**. And, they will function endocrinologically **regardless of the status of the Mullerian ducts.** So, individuals with even Mullerian agenesis will be phenotypically female with normal estrogen levels and breast development.

Question 27

Once a Mullerian anomaly is confirmed, women must also be evaluated for \_\_\_, which tend to occur with Mullerian anomalies.

Answer 27

Once a Mullerian anomaly is confirmed, women must also be evaluated for **renal anomalies**, which tend to occur with Mullerian anomalies.

Question 28

Women with unicornuate uterus are at risk for \_\_\_

Answer 28

Women with unicornuate uterus are at risk for **retromenstruation** Endometriosis in the non-communicating portion of the uterus may result in blood back-up into the peritoneal cavity

Question 29

Gold standard for diagnosing uterine anomalies

Answer 29

MRI

Question 30

Order of female egg cell progenitors in oogenesis

Answer 30

1. Oogonium 2. Primary oocyte 3. Secondary oocyte

Question 31

By week \_\_\_, the embryo is referred to as a fetus

Answer 31

By week **9**, the embryo is referred to as a fetus

Question 32

Site of fetal hematopoiesis over time

Answer 32

Question 33

"Periods" of development

Answer 33

Embryonic: Wk 1-8 Fetal: Wk 9-birth

Question 34

The time from fertilization to implantation of the blastocyst is approximately. . .

Answer 34

. . . **1 week**

Question 35

The major event that takes place during week 3 of embryogenesis

Answer 35

Gastrulation begins w/ formation of primitive streak and primitive node

Question 36

The yolk sac and amnion develop. . .

Answer 36

. . . **simultaneously during week 2 of embryogenesis**

Question 37

Role of serotonin in early gastrulation

Answer 37

Serotonin regulates the **orientation of mesoderm** development during gastrulation, effectively deciding which end forms the head. It drives expression of the NODAL gene (**no**rmal **d**evelopment of **la**terality), which ensures normal left-right positioning of organs. If this is disrupted, it can lead to anatomical anomalies such as **dextrocardia**, **heterotaxy,** or **situs inversus.**

Question 38

Heterotaxy

Answer 38

* Congenital anatomical anomaly due to disruption of serotonin in week 3 of development. * Characterized by a constellation of: * **Abnormal organ laterality** (hypoplastic left or right heart syndrome) * **Cardiac defects** * **Absent spleen OR multiple spleens**

Question 39

Timeline of embryonic organ development (and consequentially, timeline of which phases of development are affected by insults at any given time)

Answer 39

Question 40

Frequent fevers or hot-tub or sauna use early in pregnancy may result in. . .

Answer 40

. . . **defects in neural tube development and microcephaly**

Question 41

A beta hCG over ___ is consistent with pregnancy (or GTD) A beta hCG over ___ is highly likely to be GTD.

Answer 41

A beta hCG over **2000** is consistent with pregnancy (or GTD) A beta hCG over **100,000** is highly likely to be GTD.

Question 42

Trophoblasts differentiate into which two cell types?

Answer 42

Cytotrophoblasts Syncytiotrophoblasts

Question 43

Steps in implantation

Answer 43

* Begin on day 6-7 * **Apposition:** Loose connection forms between trophoblasts and endometrium * **Adhesion:** Blastocyst anchors to the endometrium * **Invasion:** Trophoblasts invade maternal capillaries to form the maternal-fetal circulation

Question 44

Resumption of Meiosis I during puberty

Answer 44

The resultant haploid oocyte arrests in metaphase II until fertilization

Question 45

5 common aneuploidys which may result in a viable fetus

Answer 45

* Down's (trisomy 21) * Edward's (trisomy 18) * Patau's (trisomy 13) * Turner's (45, X) * Kleinfelter's (47, XXY)

Question 46

A fertilized zygote will remain in the zona pellucidum as it divides to the 2-cell, 4-cell, 8-cell stage, etc. *until*. . .

Answer 46

. . . **it reaches the uterus as a blastocyst** Here **endometrial proteases** will break down the zona pellucidum This step helps avoid ectopic pregnancy and facilitates proper implantation of the trophoblasts into the endometrium

Question 47

Blastocyst to amnionic-fetal unit

Answer 47

Question 48

All dizygotic twins are __ \_\_ during development

Answer 48

All dizygotic twins are **dichorionic,** **diamniotic** during development

Question 49

Timing of the split of monozygotic twins and resultant chorionicity and amnionicity

Answer 49

* **First 3 days after fertilization**: (prior to morula stage) _Dichorionic, diamniotic_ * **Days 4-8 after fertilization:** (after trophoblast differentiation, before amnion has formed) _Monochorionic, diamniotic_ * **Days 8-12 after fertilization**: (after differentiation of the chorion and amnion, but before formation of embryonic disk) _Monochorionic, monoamniotic_ * **Day 13 or later:** (after formation of embryonic disk) _Monochorionic, monoamniotic, conjoined_

Question 50

Diagnosing dichorionic pregnancies

Answer 50

* Observance of the **lambda sign** on ultrasound: * Visualizing the septum between two separate chorions * Most specific between 10-14 weeks

Question 51

Diagnosing monochorionic diamniotic pregnancies

Answer 51

* Visualization of the thin membrane between two amnionic sacs on ultrasound:

Question 52

Diagnosing monochorionic monoamniotic pregnancies

Answer 52

No lambda sign or thin amniotic dividing membrane on ultrasound

Question 53

Possible complications of twin pregnancies

Answer 53

* Uneven distribution of nutrients: * **Dichorionic** by mechanism of **unequal placentation** * **Monochorionic** by mechanism of **uneven chorio-fetal flow** or **anastamoses**

Question 54

Complication unique to monochorionic twins

Answer 54

* **Twin-to-twin transfusion syndrome** * AV anastamosis in the chorion Results in a unidirectional blood shunt from one twin to the other * Interventions: * Laser ablation of anastamosis * Septostomy * Amnioreduction * Selected reduction

Question 55

Complication unique to non-conjoined monochorionic monoamniotic twins

Answer 55

Higher prevalence of fetal cord entanglement and intrauterine death due to the presence of two cords in the same amnion

Question 56

When does amniotic fluid start to be produced?

Answer 56

~16 weeks gestation In otherwords, this is when the fetal kidneys start producing urine!

Question 57

The corpus luteum is the main source of progesterone until about ___ weeks gestation

Answer 57

The corpus luteum is the main source of progesterone until about **10** weeks gestation Therefore, if the corpus luteum is removed prior to ~10 weeks EGA, exogenous progesterone is needed to maintain a pregnancy. However, if it is removed following ~10 weeks EGA, the placenta can take over without exogenous help.

Question 58

Risk of congenital defects for infants delivered by "true" gestational diabetics

Answer 58

Since gestational diabetes trypically does not cause a substantial elevation in blood glucose until ~2nd term, blood glucose levels are relatively normal during organogenesis, which is the time when these anomalies first develop. So, if an individual has "true" gestational diabetes, their rate of congenital anomalies is approximately the same as that of the general population. For the same reason, true diabetics with tightly-controlled blood glucose and an A1c \< 7% at the beginning of their pregnancy are not at increased risk either.

Question 59

If beta-hCG is above \_\_\_, you should be able to see a viable intraterine pregnancy if one is present.

Answer 59

If beta-hCG is above **2000**, you should be able to see a viable intraterine pregnancy if one is present. Otherwise, it is likely ectopic or non-viable

Question 60

Management of threatened abortion

Answer 60

Question 61

Progesterone in viable vs nonviable gestations

Answer 61

Progesterone **\> 25 ng/mL** almost always indicates **viable** intrauterine gestation Progesterone **\< 5 ng/mL** almost always indicates **nonviable** gestation

Question 62

After ANY delivery or abortion, you should ALWAYS follow. . .

Answer 62

. . . **hCG until it reaches zero** For a completed abortion it should halve every 48-72 hours. If they plateau, this likely indicates retained tissue (incomplete abortion OR ectopic pregnancy) and the cervix will often remain partially open

Question 63

The defining historical feature in distinguishing between inevitable abortion and cervical insufficiency

Answer 63

The presence or absence of uterine contractions Present in abortion, absent in cervical insufficiency

Question 64

Management of spontaneous abortion and cervical insufficiency based on clinical history

Answer 64

* Premature cervical dilation without passage of material or contractions: **Cervical insufficiency, treat w/ cerclage** * Premature cervical dilation without passage of material and with ongoing contractions: **Inevitable abortion, follow hCG and cervical status** * Premtaure cervical dilation without passage of material and with contractions which have since stopped: **Missed abortion, treat with D&C** * Premature cervical dilation with passage of material and with ongoing contractios: **Incomplete abortion, treat with D&C**

Question 65

Indications for using methotrexate for an ectopic pregnancy

Answer 65

* 100% certainty of the diagnosis (visualization of an adnexal or ectopic mass on ultrasound) * Features of ectopic make it susceptible: * Size \< 3.5 cm * No heart tones * bHCG \< 5000 mIU/mL