The following statement(s) is/are true about the pathophysiology of miscarriage:

• a)
  

  The onset of the maternal intraplacental circulation is both precocious and disorganised

  
  
• b)
  

  In about 2/3 of miscarriages extravillous trophoblast invasion is superficial, and plugging of the spiral arteries is less complete

  
  
• c)
  

  Markers of oxidative stress are found in both the central and peripheral parts of the placenta,

  
  
• d)
  

  In the early placenta, the villous trophoblast is less sensitive to oxidative stress than later on

  
  
• e)
  

  Selenium deficiency, which will reduce the efficacy of glutathione peroxidase, is associated with miscarriage

The following statement(s) is/are true about placental oxidative stress and late pregnancy disorders:

• a)
  

  Both oxidative stress and the systemic inflammatory response are observed to a much greater degree in pre-eclampsia

  
  
• b)
  

  Recent trials of vitamins C and E in a number of different settings have proved successful in reducing the risks of pre-eclampsia

  
  
• c)
  

  Women with a high dietary intake of vitamin C have been reported to have a trend towards an increased risk of pre-eclampsia

  
  
• d)
  

  The majority of cases of IUGR have a genetic or infectious aetiology

  
  
• e)
  

  Oxidative stress has not been implicated in PROM

The following statement(s) is/are true about oxidative stress:

• a)
  

  Hydrogen peroxide is the most commonly produced free radical in cells

  
  
• b)
  

  The high reactivity of free radicals is due to their unpaired electron

  
  
• c)
  

  Production of oxygen free radicals and oxidative stress is increased by both hyperoxia and hypoxia

  
  
• d)
  

  Production of free radicals is inhibited by the presence of free iron ions

  
  
• e)
  

  Free radicals cause protein mis-folding by breaking disulphide bonds

The following statement(s) is/are true about the baboon, which is a potential model for human placenta:

• a)
  

  The blastocyst penetrates the uterine epithelium

  
  
• b)
  

  A decidua capsularis covers the developing embryo

  
  
• c)
  

  Connections persisting between the villi and the true intervillous space are not present until late in pregnancy

  
  
• d)
  

  Trophoblast invasion occurs only by the endovascular route

  
  
• e)
  

  Trophoblast is found in spiral arteries within the inner third of the myometrium

Which of the following statement(s), often found in the current literature on pre-eclampsia, is/are true?

• a)
  

  Among the primates, only the human shows deep trophoblast invasion into the inner myometrium

  
  
• b)
  

  In humans the spiral artery smooth muscle is replaced

  
  
• c)
  

  In humans the elastic lamina of the spiral arteries is replaced

  
  
• d)
  

  Impaired deep invasion is a possible cause of pre-eclampsia

  
  
• e)
  

  Pre-eclampsia only occurs in the human

The following statement(s) concerning the effector cells of spiral artery remodelling is/are true:

• a)
  

  Vascular remodelling is exclusively affected by the action of invading trophoblast

  
  
• b)
  

  During remodeling the vascular smooth muscle undergoes vacuolization

  
  
• c)
  

  During remodeling both the endothelium and the vascular smooth muscle become swollen

  
  
• d)
  

  This remodelling process involves a replacement of the maternal endothelium by endovascular trophoblast for the remainder of the pregnancy

  
  
• e)
  

  Intramural invasion of the spiral arteries by trophoblasts results in a widened vessel that no longer shows any vasomotor activity

The following statement(s) concerning interstitial trophoblast invasion is/are true:

• a)
  

  Interstitial invasion is exclusively affected by multinuclear giant cells, derived from the primitive syncytium, which is formed in the wall of the implanted blastocyst

  
  
• b)
  

  Interstitial trophoblasts are derived from extravillous mononuclear cytotrophoblast

  
  
• c)
  

  The onset of interstitial mononuclear trophoblast invasion corresponds with the breakdown of the cytotrophoblastic shell

  
  
• d)
  

  After their invasion of the inner myometrium, interstitial trophoblasts surround the spiral arteries, invade the vessel walls and become intravascular

  
  
• e)
  

  During their invasion of the inner myometrium, interstitial trophoblasts contribute to the weakening of the vascular smooth muscle of the spiral arteries, preparing the vessels for a deep invasion by a separate endovascular subset of invasive trophoblast

Regarding the timing of remodelling of the utero-placental arteries

• a)
  

  During the first trimester, only the decidual segments of the spiral arteries are invaded and remodelled

  
  
• b)
  

  Endovascular invasion of the myometrial segments only begins after 20 weeks

  
  
• c)
  

  With trophoblastic remodelling invaded trophoblast is embedded in a fibrinoid extracellular matrix

  
  
• d)
  

  Maximum maternal perfusion is reached when deeper vascular invasion is established

  
  
• e)
  

  During the third trimester, re-endothelialization occurs in the spiral arteries

The following is/are important normal event(s) during vascular adaptation to pregnancy:

• a)
  

  Increased influx of immune cells, including uterine natural killer cells

  
  
• b)
  

  Decreased vascular permeability

  
  
• c)
  

  Remodelling of veins

  
  
• d)
  

  Creating high-resistance vessels

  
  
• e)
  

  Branching angiogenesis throughout gestation

The vascular pattern in human decidua changes as gestation progresses. These vascular changes include which of the following:

• a)
  

  Apoptotic death of maternal vascular smooth muscle cells.

  
  
• b)
  

  Loss of vascular smooth-muscle cells surrounding vessels

  
  
• c)
  

  Increased vessel density

  
  
• d)
  

  Decreased luminal diameter

  
  
• e)
  

  Increased total vessel surface

The following descriptions are characteristic for angiogenic growth factor:

• a)
  

  Placental growth factor is particularly involved in regulating vascular remodelling in the decidua basalis

  
  
• b)
  

  Angiopoietin-1 is involved in the maturation of the vasculature

  
  
• c)
  

  Vascular endothelial growth factor-A is not able to induce trophoblastproliferation and migration

  
  
• d)
  

  Angiopoietin-2 stimulates sprouting angiogenesis

  
  
• e)
  

  MT2-MMP is the best known MT-MMP engaged in tumour metastasis and angiogenesis

Vascular patterns and its regulation in compromised pregnancies include:

• a)
  

  Increased branching angiogenesis in intrauterine growth restriction

  
  
• b)
  

  Slowly developing vascular network in miscarriage

  
  
• c)
  

  Too superficial infiltration of endovascular trophoblasts in pre-eclampsia

  
  
• d)
  

  Production of soluble pro-angiogenic factors by the placenta in pre-eclampsia

  
  
• e)
  

  Differential decidual expression of various angiogenic factors in miscarriage

The following statement(s) is/are true about current screening for pre-eclampsia:

• a)
  

  Screening based on maternal risk factors and history will identify 60% of women destined to develop pre-eclampsia.

  
  
• b)
  

  Second-trimester uterine artery Doppler will identify 55% of women destined to develop pre-eclampsia.

  
  
• c)
  

  The World Health Organization (WHO) recommends likelihood ratios for a positive predictive test and negative test are greater than 10 and less than 0.1, respectively.

  
  
• d)
  

  WHO- recommended likelihood ratios for a positive predictive test and negative test are greater than 5 and less than 0.5, respectively.

  
  
• e)
  

  Only a few individual biomarkers when used in isolation have clinical value in the prediction of pre-eclampsia.

In the first trimester in women who subsequently develop pre-eclampsia, compared with women at the same gestation who do not, the following statement(s) about biomarkers is/are true:

• a)
  

  Levels of PAPP-A and PP-13 are reduced

  
  
• b)
  

  PAPP-A is elevated and PP-13 reduced

  
  
• c)
  

  sFlt 1 levels are elevated

  
  
• d)
  

  sFlt 1 levels are elevated and sEng reduced

  
  
• e)
  

  PlGF levels are reduced

The following statement(s) is/are true about prophylactic or preventative treatments of pre-eclampsia:

• a)
  

  Antioxidants are of value in high-risk women but are of no benefit in healthy low-risk pregnancies.

  
  
• b)
  

  Low-dose aspirin confers a 10% risk reduction for developing pre-eclampsia.

  
  
• c)
  

  Additional benefits can be gained in the reduction of pre-eclampsia in high-risk women by using a high-dose aspirin regimen.

  
  
• d)
  

  Calcium supplementation has the same beneficial effect in risk reduction regardless of dietary intake.

  
  
• e)
  

  Calcium supplementation seems to be of greater benefit in younger women aged under 20 years.

The following statement(s) is/are true about risk factors for pre-eclampsia?

• a)
  

  Previous pre-eclampsia is a strong risk factor

  
  
• b)
  

  Recurrence risk is inversely related to gestational age at first delivery.

  
  
• c)
  

  High maternal body mass index (BMI) is a strong risk factor

  
  
• d)
  

  Primiparity is a strong risk factor

  
  
• e)
  

  Smoking is a strong risk factor

For which of the following is/are their some evidence of benefit for use in the prevention of pre-eclampsia?

• a)
  

  Fish Oil

  
  
• b)
  

  Vitamin C and E

  
  
• c)
  

  Low-dose aspirin

  
  
• d)
  

  Diuretics

  
  
• e)
  

  Antidepressants

When uterine artery Doppler is being used in the prediction of pre-eclampsia, which finding(s) is/are most likely to be associated with the development of pre-eclampsia?

• a)
  

  Increased diastolic flow

  
  
• b)
  

  Diastolic notching

  
  
• c)
  

  Decreased resistance index

  
  
• d)
  

  Decreased pulsatility index

  
  
• e)
  

  Peak systolic velocity > 1.5 MoM

Which of the following statement(s) about pre-eclampsia and intrauterine growth restriction (IUGR) is/are correct?

• a)
  

  An adequate screening test for pre-eclampsia and IUGR is currently available.

  
  
• b)
  

  Treatment with aspirin at any stage in gestation has been shown to decrease the risk of developing pre-eclampsia and IUGR.

  
  
• c)
  

  The pathophysiology of pre-eclampsia and many cases of IUGR is thought to include the abnormal trophoblast-mediated modification of the spiral arteries in early pregnancy.

  
  
• d)
  

  The placentas in pre-eclamptic and IUGR pregnancies show decreased resistance to blood flow compared with those in normal pregnancies.

  
  
• e)
  

  Inadequate spiral artery modification is seen only in cases of pre-eclampsia when IUGR is also present.

Which of the following statements about uterine artery Doppler is correct?

• a)
  

  First-trimester uterine artery Doppler is superior to second-trimester uterine artery Doppler in identifying women at risk for the development of pre-eclampsia and IUGR.

  
  
• b)
  

  Increased placental resistance as detected by uterine artery Doppler has been correlated with abnormal trophoblast invasion of the spiral arteries on histopathology.

  
  
• c)
  

  Uterine artery Doppler provides a direct measurement of placental vascular resistance.

  
  
• d)
  

  Presence of a diastolic notch in the third trimester has been associated with a decreased risk for pre-eclampsia.

  
  
• e)
  

  Measurement of uterine artery Doppler has been shown to have poor reproducibility.

Which of the following statements about spectral Doppler of the spiral arteries is correct?

• a)
  

  Spiral artery spectral Doppler is not feasible in early pregnancy.

  
  
• b)
  

  Elevated resistance index of the spiral arteries is highly sensitive for the detection of pre-eclampsia and IUGR.

  
  
• c)
  

  Studies evaluating the use of spectral Doppler of the spiral arteries in early pregnancy were limited by small numbers of participants, heterogeneous study groups, and poor reproducibility of the technique.

  
  
• d)
  

  The spiral artery Doppler waveform has a similar appearance to the uterine artery Doppler waveform.

  
  
• e)
  

  Spiral artery spectral Doppler seems to be less sensitive to the prediction of IUGR in later compared with earlier pregnancy.

Which of the following statement(s) about three-dimensional power Doppler (3DPD) angiography of the utero-placental circulation space (UPCS) using the Virtual Organ Computer-Aided Analysis™ software is/are correct?

• a)
  

  3DPD angiography of the UPCS provides a more direct means of evaluating the UPCS compared with uterine artery Doppler and three-dimensional placental volume.

  
  
• b)
  

  Standardised ultrasound settings for 3DPD angiography of the placenta have been published.

  
  
• c)
  

  3DPD angiography of the UPCS is a promising technique for future screening for pre-eclampsia and IUGR.

  
  
• d)
  

  3DPD flow parameters have been correlated with actual blood flow in an in-vivo sheep model.

  
  
• e)
  

  Studies in humans have shown good reproducibility of the 3DPD technique.

Which of the following is/are correct:

• a)
  

  The spiral arteries have a myometrial segment and a decidual segment

  
  
• b)
  

  The decidual segment of the spiral arteries can be examined by studying the basal plate of the placenta

  
  
• c)
  

  The myometrial segment of the spiral arteries can be studied by examining the basal plate of the placenta

  
  
• d)
  

  The myometrial segment of the spiral arteries can be studied by examining a placental bed biopsy or a hysterectomy specimen

  
  
• e)
  

  The diagnosis of disorders of deep placentation requires histologic examination of the placental bed, containing myometrium and at least one spiral artery

What histological finding(s) may be used to determine whether a specimen is obtained from the placental bed

• a)
  

  Vascular smooth muscle around the non-transformed vessels

  
  
• b)
  

  Interstitial trophoblasts

  
  
• c)
  

  Fibrinoid material around the non-transformed vessels

  
  
• d)
  

  Macrophages or uterine natural killer cells

  
  
• e)
  

  Decidual vessels

What is/are the histological finding(s) in a placental bed biopsy specimen or in the basal plate of the placenta of patients with preterm labor with intact membranes that differ from patients who deliver at term?

• a)
  

  Higher frequency of non-transformed vessels in the myometrial segment of the spiral arteries from the placental bed biopsy specimens

  
  
• b)
  

  Higher frequency of non-transformed vessels in the decidual segment of the spiral arteries from the basal plate of the placenta

  
  
• c)
  

  Higher frequency of non-transformed vessels in the decidual segment of the spiral arteries from the placental bed biopsy specimens

  
  
• d)
  

  Lower frequency of non-transformed vessels in the myometrial segment of the spiral arteries from the placental bed biopsy specimens in cases with chorioamnionitis

  
  
• e)
  

  Lower frequency of non-transformed vessels in the decidual segment of the spiral arteries from the placental bed biopsy specimens in cases with chorioamnionitis

Failure of physiologic transformation of the spiral arteries have been reported in the following obstetric conditions:

• a)
  

  Spontaneous second trimester miscarriage

  
  
• b)
  

  Preterm labor with intact membranes

  
  
• c)
  

  Preterm prelabor rupture of membranes

  
  
• d)
  

  Abruptio placentae

  
  
• e)
  

  Unexplained fetal death

Successful implantation is thought to be controlled by which of the following factor(s):

• a)
  

  Sex steroids hormones

  
  
• b)
  

  Peptide hormones

  
  
• c)
  

  Growth factors

  
  
• d)
  

  Cytokines

  
  
• e)
  

  Immunological factors

The following statement(s) is/are true concerning prostaglandins and pregnancy:

• a)
  

  Concentrations of endogenous prostaglandins in human decidua are lower in pregnancy than in the endometrium at any stage of the menstrual cycle

  
  
• b)
  

  Concentrations of endogenous prostaglandins are principally determined at this time by increased or decreased metabolism

  
  
• c)
  

  An inability to metabolise prostaglandins is associated with early pregnancy loss

  
  
• d)
  

  Prostaglandin level changes are similar in ectopic and intrauterine pregnancy

  
  
• e)
  

  Prostaglandin levels are most likely mediated by local rather than systemic means in early pregnancy

The following statement(s) is/are true concerning prostaglandins and progesterone:

• a)
  

  Most evidence suggests the progesterone is the most likely steroid responsible for prostaglandin (PG) regulation

  
  
• b)
  

  Progesterone is thought to have an effect on PG production directly by inhibiting the release of arachidonic acid from endometrial cells

  
  
• c)
  

  Progesterone is thought to have an effect on PG production indirectly by up-regulating inhibitors of prostaglandin synthesis

  
  
• d)
  

  Progesterone is not thought to have an effect on PG receptor activity

  
  
• e)
  

  The mode of action of progesterone seems to be completely dependent on its interaction with either progesterone or glucocorticoid receptors

The following is/are true concerning regulation of prostaglandins in the decidua:

• a)
  

  Secretory protein-A is considered important in the regulation of prostaglandin production

  
  
• b)
  

  Surfactant protein-A is considered important in the regulation of prostaglandin production

  
  
• c)
  

  The rate-limiting step in the synthesis of prostaglandins is the hydrolysis of non-esterified arachidonic acid from membrane phospholipid

  
  
• d)
  

  PG release is mediated primarily by the phospholipase A ₂ enzyme

  
  
• e)
  

  PG production is primarily from the glandular epithelial cells in the decidua