Pregnancy Flashcards
Risk of down syndrome by age at Delivery
Down at delivery: 35=1:350, 40=1:100, 45=1:30, 50=1:10
Quad screen testing
T21 (75%):
HCG/Inhibin ↑
uE3/MSAFP ↓
T18 (65%): HCG/uE3/MSAFP ↓
Inhibin N/A
ONTD (85%): ↑ MSAFP
Quad screen does not screen for T13
VTE risk in pregnancy
5-20/10,000 woman years
Molar pregnancy
What enzyme does fetus lack?
3 B OH dehydrogenase
What enzymes does placenta lack?
17a hydroxylase
17, 20 lyase
16a hydroxylase
Three levels of sexual differentiation
o 1- Chromosomal sex: XY, XX, XXY (Klinefelter’s), X0 (Turner’s), XXY
o 2- Gonadal sex: ovary/testes/gonad
o 3- Phenotypic sex: androgens/estrogens
Male development
+SRY SOX9 promotes Sertoli cells, desert hedghehog promotes leydig cells differentiation, T prodn drives male development, DHT: penile length, prostate
Female development
driven by absence of -AMH, also WNT4, RSPO1 B-catenin, HOX genes*
o DES alters HOX gene expression, is mechanism of T-shaped uterus, vaginal adenosis in affected females
HOX genes
- HOXA9: fallopian tubes
- HOXA10: uterus
- HOXA11: Uterus and cervix
- HOXA13: vagina
Virilized female infant
o CAH: 21-alpha hydroxylase, 11-beta hydroxylase (both have high DHEA, androstenedione), 3-beta HSD (mildly virilized, elevated DHEA)
o Maternal androgen prodn
Luteoma (30% women virilized, of virilized moms 80% have virilized fetus)
Sertoli-Leydig tumor (highest risk virilization)
Placental aromatase deficiency (progressive virilzation of mother then baby)
Drugs
When is uterine and vaginal development complete?
16 weeks
When does T production start
8 weeks
8-9 weeks regression of Mullerian ducts
when is male external genitalia complete?
9-14 weeks prostate and external genitalia developed under T and DHT influence
CAH and female genitalia
female external genital development not done until 20 weeks
elevated androgen levels between 10-12 weeks lead to clitoromegaly, labial fusion, and partial closure of the urethra
Dose of folic acid with history of NTD
4 mg
Neonatal treatment of CAH
adrenal crisis is an emergency
hypotension, hyponatremia, hyperkalemia, hypoglycemia, n/v, weight loss, anorexia
Treatment: fluids (0.9%tes, NS 10-20 mL/kg)
electrolytes (correct electrolytes with long term NaCL)
Corticosteroids and mineralocorticoids
P450 Oxidoreductase deficiency
AR caused by missense mutation
affects all P450 enzymes with variable phenotype
Antley Bixler syndrome
craniosynostosis, midface hypoplasia, choanal atresia or stenosis, radiohumeral or radioulnar syntostosis, femoral bowing and fractures, and joint contractures
type of P450 oxidoreductase deficiency
Hormone levels with P450 oxidoreductase deficiency
Basal/stimulated:
17 OHP: high, exaggerated
DHEA/S: low, low
Androstenedione: low, low
Cortisol: low, normal
luteoma
hyperplastic masses of luteinized cells
average 6-10 cm, 1/2 are bilagteral
1/3 have maternal hirsutism/virilization
80% of infants with virilized mothers are also virilized
Regression after delivery, but maternal virilization may not regress
Theca lutein cysts
type of functional cyst
10-15 cm
usually bilateral
regression post deliver
common in women with GTD, molar pregnancies, multiple gestation
mass effect, pain
fetus is NOT virilized
Aromatase deficiency
fetal androgens are not converted to estrogens in the placenta causing low maternal estrogen
Androgen insensitivity syndrome
X linked
Defective T receptor
Testes will develop normally but do not descend (found in inguinal canal)
without T response you get regression of wolffian ducts (internal male genitalia), but also AMH is present so you get regression of mullerian ducts
What mediates abdominal transport of testes
AMH
What mediates inguinal transport to scrotum
Testosterone
Hormonal profile of AIS
High LH
normal to high T
high E (for men)
management of intraabdominal gonads or streak gonads with Y chromosome
Remove
high risk of malignancy which increases at puberty
exception is AIS which you should leave until completion of puberty
gonadoblastoma and dysgerminoma
Generally risk is 5-10% and incidence increases after 25 yo
5a reductase deficiency
AR
deficient DHT type II
genotype is XY and phenotype is XX to somewhat ambiguous
Pseudo female external genitalia (hypospadias, varying degrees of fusion of labioscrotal folds, urogenital opening) with separate vaginal and urethral openings
No mullerian ducts
present wolfian ducts and cryptorchidism
reared as females, but masculization occurs at puberty with less facial and body hair, less temporal balding, no acne
Diagnosis of 5a reductase deficiency
elevated T: DHT radio
HCG stim test 1500 mIU on d1 and d3, measure T and DHT on 1, 3, and 6
this helps to distinguish between 5a reductase and defects in T synthesis and incomplete AIS
Treatment of 5a reductase deficiency
gonadectomy before puberty to avoid neoplasia and virilization at puberty
versus early diagnosis could allow for correction of hypospadias, cryptorchidism for male rearing and fertility (+spermatogenesis)
AMH or AMH R disorder
normal male with inguinal hernia with mullerian structures (hernia uterine inguinale syndrome)
45% caused by mutation in AMH gene and 39% in AMH-R gene
Swyer syndrome
XY gonadal dysgenesis
no SRY
no AMH and no testosterone
have mullerian ducts and female external genitalia
but you do have streak gonads which should be removed
raised as female
How can true hermaphroditism occur
- division of 1 ovum with fertilization of each haploid ovum and then fusion of the two zygotes early in development
- ovum fertilized by 2 sperm with trisomic rescue to form normal diploid complement
- 2 ova fertilized by 2 sperm (1 male and 1 female zygote) that fuse to form a tetragametic chimera
- mutation in SRY gene
trisomic rescue
genetic phenomenon when fertilized ovum contains 3 copies of a chromosome and then loses one of these chromosomes to form a normal, diploid, chromosome complement
evaluation of ambiguous genitalia
size of phallus (clitoris 2-6 mm is normal, 9 mm is clitoromegaly)
position of urethral meatus
palpation of gonads
fused or separated labio scrotal folds (fused scrotum, separated is labia)
hyperpigmentation could indicated increased ACTH and adrenal defect
