genetic diseases

Question 1

Primary ovarian insufficiency - POI - Depletion or dysfunction of
ovarian follicles with cessation
of menses before age 40.

Answer 1

Affects ~1% of women
under 40 years old. &
~0.1% under 30 yrs

Question 3

Basic Inheritance

Answer 3

 Genetic mutations:
 Dominant: one copy of
mutation can pass this disease
on to future generations.
 Recessive: Disease only occurs
when two copies of the gene
are inherited (one from each
genetic contributor).
 X-Linked: Mutation found on
the X-Chromosome. Disease
usually occurs in males since
they only have one Xchromosome.

Question 4

Primary ovarian insufficiency - POI - is it regular?

Answer 4

Ovarian function is
intermittent or unpredictable. 5-10% could have
spontaneous
conception/deliver

Question 5

Primary ovarian insufficiency - POI - what hormones do we test for? and what is the timeline?

Answer 5

FSH/ E2 are measured on at least two separate
occasions (with more than 4 weeks of
interval), elevated FSH levels (greater than 25 IU/L)

Question 6

POI - what type of genetic abnormalities?

(PO has C12)

Answer 6

Chromosomal
abnormalities, Genetic
polymorphisms, and Single
gene mutations

Question 7

POI can be Non-Genetic

(Po ME AI)

Answer 7

Autoimmune, Iatrogenic (relating to illness),
Metabolic, Infectious or
Environmental

Question 8

genetic screening policy - Spring will offer comprehensive, expanded panel genetic carrier screening to
all patients.

Answer 8

 Horizon 421- natera
 A decision regarding completing–Horizon 421 is required for genetic
contributors pursuing ovulation induction, IVF and/or frozen embryo
transfers (if not completed prior to embryo cryopreservation). Genetic
carrier screening is encouraged but not required for patients pursuing
oocyte cryopreservation.
 Patients with prior ECS screening, see Acceptable panels
chart (CN11). Those who completed acceptable panel do
not need to sign a waiver and are NOT encouraged to
complete Natera 421
 If panel not listed, we will recommend H421 or
waiver.
 Expanded panel carrier screening cannot be waived by gamete donors
managed by Spring. This includes identified sperm donors, identified
and non-indentified ovum donor’s and spring’s egg bank, Nest, ovum donors

Question 9

CN 11 policy—ECS testing

Answer 9

Treatment should not be started until one of the scenarios is met:
 Testing has been waived/declined
 “Extended genetic carrier screening waiver” signed both genetic contributors
 Testing Complete: Negative Result (s)
 Oocyte contributor alone or both gamete contributors
 Testing Complete: Positive Result(s)
 Discordant (both tested NOT carriers of same conditions)
 Oocyte contributor tested, positive is NOT on “No Go” List & Partner NOT testing
 15 min. call w/GC required ($100) & Sign waiver
 Both positive for same mutation & complete proper follow up
 See CN 11 for all variations of positive results and proper follow up

Question 10

X link is only tested in the

Answer 10

provider

Question 11

carrier screening results pending - One or both results pending and proceeding with Tx.

Answer 11

Alert must be added to chart: “PENDING HORIZON”
* They must sign an appropriate waiver.
* Not applicable if results from one genetic contributor are positive
for a condition on Spring’s “No Go” list then they must wait for
pending results of the other genetic contributor.

Question 12

Pending Genetic Carrier Screening waiver:

Answer 12

• IUI
• IVF
• NOTE: NYC- Patients are NOT allowed to proceed with treatment
  with pending results, this waiver is not applicable at that site.

Question 13

The “NO GO” Genetic Diseases
(no go CT FGS) (cat no go fgs)

Answer 13

Cystic Fibrosis
 Tay-Sachs
 Fragile X Syndrome
 Gaucher
 Spinal Muscular Atrophy

Question 14

Cystic Fibrosis

Answer 14

Cystic fibrosis is a progressive disease
that affects the lungs, pancreas and
other organs. - won’t be tested on this

Question 15

In people with
CF, mutations in the cystic
fibrosis transmembrane
conductance regulator
(CFTR) gene cause the CFTR
protein to become
dysfunctional.13

Answer 15

*No cure, treatment can ease
symptoms, reduce complications
and improve quality of life
*Congenital bilateral absence of the
vas deferens (CBAVD) is found in 1%
to 2% of males with infertility and is
present in 6% of
obstructive azoospermia cases.
*Nearly 95% of men with cystic fibrosis have CVAD

Question 16

Tay-Sachs

(Tay is fat)

Answer 16

Caused by an absence of an enzyme(betahexosaminidase A) that helps break down fatty
substances (GM2 gangliosides) in the body.
 Toxic levels of gangliosides in the brain and
spinal cord affect the function of nerve cells.
 Three forms of Tay-Sachs
 Infantile (most common)-survival only
a few yrs
 Juvenile (range of severity)-survival
into teen yrs.
 Late onset/adult (least severe/less
common)
 No cure, only treatments to relieve
symptoms and increase quality of life
 Ashkenazi Jewish descent are commonly at
risk

Question 17

POI usually have low levels of

Answer 17

estrogen - so bone problems, etc.

Question 18

concordancy

(concordant diseases)

Answer 18

both providers positive for the same disease - absolutely need genetic counseling if this is the case

Question 19

PGTA

(A line up)

Answer 19

autosomal - just lining up

Question 20

PGTM - when to do it?

Answer 20

when one is a carrier

Question 21

Fragile X Syndrome

(fragile autism)

Answer 21

 Affects 1 in every 4,000 males and 1 in every 6-8,000 females
 Leading known genetic cause of autism

More often the egg provider that has fragile X
 Causes a range of developmental problems, learning disabilities, and
cognitive impairment
 Physical features:
 long and narrow face
 large ears
 a prominent jaw and forehead
 unusual flexible fingers
 flat feet in males

Question 22

Fragile X Syndrome,
cont. (continued)

(fragile X is the former 1 brain)

Answer 22

Defect in the FMR1 Gene on
the X- Chromosome.
 This protein is required for the
brain to develop normally.
(synapses->nerve cells)
 Fragile-X mutation-> FMR1
gene is switched OFF due to
excessive CGG repeats

premutation - 55-199 # of CGG repeats - some symptoms reported - always need genetic counseling if this is the case

Question 23

Gaucher Disease

(gaucho has a big belly)

Answer 23

Individuals are missing an enzyme that would break down lipids
Main Symptoms:
 Swollen belly - enlargement of spleen and liver
 Bone pain and easily fractured bones
 Anemia, low blood counts and fatigue
 Bleeding and bruising problems
Types:
1: most common, treatable, and normal brain development
2: rare, severe neurological abnormalities, fatal within the first 2
years
3: slower onset than type 2 and some survive until adulthood

Question 24

Spinal Muscular Atrophy

Answer 24

Degeneration of motor neurons
 Damages and kills specialized nerve cells in the brain and spinal cord
 Leads to progressive muscle weakness and atrophy
 Depending on the type, severity can lead to death
 most common is type I (Werdnig-Hoffman disease)
 Type 1 usually evident at 6 months of age
 No cure
 Treatment helps to lessen symptoms
 Other symptoms:
 Muscle atrophy
 Arthritis
 Trouble breathing
 Trouble eating or swallowing

Question 25

Familial
Dysautonomia

(dys breathing)

Answer 25

Impacts autonomic and sensory neurons
* Involuntary actions such as breathing, body
temperature and blood pressure regulation, and
digestion are greatly affected
* Most common in those of Ashkenazi Jewish descent
* Symptoms begin in infancy, worsen with age
* Difficulty swallowing
* Frequent choking/gagging
* Poor weight gain
* Frequent lung infections
* No tear flow when crying
* Decreased reflexes/muscle tone
* Scoliosis
* No cure
* treatment exists to relieve symptoms and
prevent complications

Question 26

Canavan

(caravan the sponges)

Answer 26

Autosomal recessive inheritance pattern
 Most common in those of Ashkenazi Jewish descent
 Damages the ability of nerve cells (neurons) in the
brain to send and receive messages.
 Weak muscle tone and enlarged head size
 Characterized by the spongy degeneration of white
matter in the brain.
 Loss of motor skills including head support, sitting skills,
feeding/swallowing difficulties, and seizures.
 Life expectancy varies on severity of disease.

Question 27

Hemoglobinopathies

Answer 27

Hemoglobin (Hb), the pigment in RBCs that transfers oxygen to tissues, changes structure during human
development. An inherited disorder that affects the number or shape of red blood cells in the body-
> Hemoglobinopathy
 Inherited hemoglobin disorders fall into two main groups:
 Structural hemoglobin variants -in some cases they may alter the stability or functional properties of the
hemoglobin and lead to a clinical disorder
 Ex. Sickle cell anemia
 Thalassemias –classified according to the ineffectively synthesized globin chain. (alpha/beta).
 With the exception of the few patients who can obtain a bone marrow transplant, no cure exists for the inherited
disorders of hemoglobin.
 Treatment depends on the inherited disease.

Question 28

Horizon - need to know this

Answer 28

Okay to check off “Horizon” on checklist when:
 Egg freeze patient – not required, therefore can be signed off at
any point
 Patient/Partner results are negative/normal
 Results for patient and partner/sperm source are both resulted and
confirmed either one is normal/negative, or they are discordant. If
using a sperm donor-these results must be cross-checked by APP/GC
,depending on site, prior to patient purchasing/utilizing the sperm.
 If /when applicable, waiver has been signed, uploaded, and documented

Question 29

Known
variant
PGT-M

Answer 29

we need the report

Patients who come in with a known variant that they’d like to
pursue PGT
-M for still need genetic counseling with our Spring
Genetics counselors to discuss PGT
-M in detail.
 Most patients with a known variant will have had genetic
counseling regarding their condition, but most will not have had
genetic counseling to discuss the flow for creating a probe,
parental testing, and potential barriers we can run into along the
way (only “affected” embryos, neither parent positive, partner
testing, testing embryos for a VUS, etc.).
 For certain dominant genes (BRCA2 for example), there is
recessive risk as well, so discussion of optional partner testing
must be reviewed with a GC since a PGT
-M lab will not discuss this

Question 30

nest

Answer 30

is the carrier company we use

Question 31

2 consent forms if getting genetic testing

Answer 31

natera and spring consents

Question 32

natera automatically enters into

Answer 32

our system. if pt wants another lab, it gets a little more complicated. must have a good reason to use another company

Question 33

421 is for the

Answer 33

egg provider - X linked conditions

Question 34

if we have integrated results

Answer 34

click on line item and click on report - you can see report -

Question 35

any positive not on the no go list

Answer 35

that they aren’t having the partner screened for, they need to do the 15 min consult for about $100

Question 36

sperm donors not required

Answer 36

to do a formal consult, unless indicated by results

Question 37

no-go genetic diseases

(No-go HX CD)

Answer 37

 Canavan
 Familial Dysautonomia
 Hemoglobinopathies (Alpha, Beta)
 X-linked or other conditions w/1 in 2 (50%) chance