Exam 1: Red Flags/Key Phrases Flashcards
Unsafe Immunization during pregnancy
MMR, Varicella, Oral Polio, and BCG for TB
Pregnancy Category X drugs
Warfarin (coumadin) and isotretinoin (acutein). Note: Lisinopril is category D.
APA + AMA Detail
NO increase in fetal autosomal aneuploidy in APA but most common aneuploidy in AMA is autosomal trisomy
Seizure Disorder in Pregnancy
Avoid Valproate and Carbamazepine
Function of SRY and PAR1+2
SRY = Codes for TDF (testis determining factor) + Leydig/Sertoli Effects.
PAR 1 = required for XY pairing during spermatogensis
Male Sex Determination Genes + Function
SRY = most important
SRY + SF1 = upregulates SOX-9 + F6F9
SOX-9 + F6F9 = self feedback loop = male development in XY
SOX-9 = leads to change from pre-sertoli to sertoli cells
F6F9 (fibroblast growth factor) = in balance between female pathway (WNT4/RSPO/Beta-caterin) and shift to F6F9 leads to male sexual development
Note: DAX-1 = necessary for gonadal development in both sexes
Female Sex Determination Genes + Function
in XX Gonads = WNT4/RSPO/Beta-Catenin dominant SOX-9/F6F9
WNT4 Pathway = ovarian development + mullerian duct formation
RSPO1 = Binds and stabilizes Beta-caternin which regulates gene transcription. Also degrades Sox-9 in ovaries.
Note: WNT4 + RSPO1 = positive self feedback loop.
Note: Estrogen not required for female differentiation
Clinical: Campomelic Dwarf/Syndrome/Dysplasia
Poor dysfunctional bone structure due to absence of SOX-9 (control bone growth in fetus).
Female Infertility Scheme: Unexplained infertility Treatment
3-4 Cycles of Clomiphene Citrate (blocks negative feedback of hypothalamus, acts as estrogen agonist.)
Add Intrauterine insemination, 6 cycles
1-3 cycles of FSH and IUI
IVG
Female Infertility Scheme: Labs
Day 21 Progesterone (if 35 yo + FH of POF (if
Undermasculinzed Male (DSD)
(disorders of testosterone biosynthesis)
CYP450 Oxireductase Deficiency
17 alpha - Hydroxylase Deficiency
17 beta - HSD Deficiency
Ambigous Genitalia: Gonads Palpable:
46XY (normal)
CYP450 Oxireductase Deficiency = Cause of Antley Bixler Syndrome (skeletal dysplasia, ambigous genitalia, abnormal steroidgenesis)
17 alpha - Hydroxylase Deficiency = Salt and Water Retention: HTN
17 beta - HSD Deficiency = Undescended Testes
Mixed Gonadal Dysgenesis
Denys-Drash Syndrome!
Ambigous Genitalia: Gonads Palpable:
45XO/45XY = most common mosaicism (Physical = ovary and testes side, both on the same genitalia) b
Streak Gonads and Testis on opposite sides: Increase risk of wilms tumor, gonadoblastoma, and dysgerminoma
Denys-Drash Syndrome (WT1 gene mutation) - above + renal failure (nephropathy)
Mayer-Rokintansky Syndrome
Ambigous Genitalia: Gonads Not Palpable:
Mutation of WNT4 gene
Congenital absence of uterus and proximal vagina BUT Ovaries and fallopian tubes are present (normal FSH and LH)
hemochromatosis
Male Infertility: Endocrine
Genetic disorder of mucosal iron transport resulting in tissue deposition in the pituitary tissues = Decrease FSH and LH and therefore testosterone
Mumps Orchitis
Male Infertility: Testicular (primary hypogonadism)
Infection: damage to seminiferous tubules as well as leydig cell damage (decrease testosterone)
Prader Willi Syndrome
Male Infertility: Testicular (primary hypogonadism)
Most common syndromic form of obesity
Symptoms = low muscle tone in nursury
Masculinized Female (DSD)
46XX Congenital Adrenal Hyperplasia
17 OH Progesterone Elevated! (Decreased cortisol, increased testosterone)
21 Hydroxylase Deficiency: Salt wasters
Virilization in Females, “Little Hercules” in Males
TX: Dexamethasone
Normal Sperm Values
Volume = greater than or equal to 1.5 ml
Sperm Concentration = GTOET 15 million sperm/ml
Normal Morphology = GTOET 4%
Progressive Motility = GTOET 32%
Also, test if decrease fructose = associated with congenital absence of vas deferns, seminal vesicles, or ejaculatory duct obstruction.
Morning Testosterone
if Low = primary hypogonadism (testicular/anatomic)
Kallman Syndrome + Genes and Interaction
KAL1 (x linked) = loss of anosmin
KAL1 + FGFR1 interaction with Heparin
KAL1 binds to FGFR1 = inhibits binding of FGFR1 to FTFR2 + Heparin to form complex
KAL1 binds to heparin = activates and promotes dimerization via FGF2 + heparin binding.
FGF8 = ligand for FGFR1, SX: Hearing loss, high arched palate, cleft stuff.
1st + 2nd Trimester Serum Markers : Trisomy 21
1st Trimester: Trisomy 21: ↑ human chorionic gonadotropin (hCG), ↓ Pregnancy Associated Plasma Protein A (PAPP-A, metalloproteinase). 80%* (+ maternal age)
2nd Trimester: 2nd Tri Serum Markers – Trisomy 21
o Triple screen: ↓ α-fetoprotein (AFP or MSAFP), ↑ human chorionic gonadotropin (hCG), ↓ Unconjugated estriol (uE3, produced by placenta)
• Detection rate ~60%, false positive rate ~5%
o Quad screen: triple screen + ↑ dimeric inhibin A (InhA, produced by placenta, inhibits FSH)
• Detection rate ~75%
1st + 2nd Trimester Serum Markers : Trisomy 18
1st Trimester:
o Trisomy 18: ↓ hCG, ↓ PAPP-A. 90%*
o Trisomy 13: ↓ hCG, ↓ PAPP-A. 90%*
2nd Tri Serum Markers- Trisomy 18
o Triple screen: ↓ α-fetoprotein (AFP or MSAFP), ↓ human chorionic gonadotropin (hCG), ↓ Unconjugated estriol (uE3)
• Detection rate ~80%, false positive rate ~0.6%
o Not as well studied: triple screen + ↓ dimeric inhibin A (InhA)
• Preliminary results detection rate 100%, false positive rate ~0.3%
1st and 2nd Trimester Ultrasound
1st Tri Ultrasound Screen (Pictures)
o ↑ nuchal translucency: collection of fluid at the back of fetal neck
o ↑ abnormal high-impedance flow through ductus venosus
o Tricuspid regurgitation
o No visualization or hypoplasia of nasal bone
2nd Tri Ultrasound Screen
o ↑ nuchal fold = refers to the nuchal translucency
o ↓ humerus length
o Renal pelvic dilation – kidney enlargement
o Intracardiac echogenic foci – bright spots on the heart
o Choroid plexus cyst – choroid plexus produces cerebrospinal fluid “spongy layer” of cells and blood vessels
o If these things appear in isolation, doesn’t mean too much, apparently it’s common.
