Infertility/RPL Flashcards

1
Q

Describe findings of peritoneal fluid in women with endometriosis

A
  • Increased macrophages
  • Decreased cytotoxicity of NK cells
  • Increased cytotoxic and helper T cells increased
  • Increased COX-2
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2
Q

What are the epigenetic changes found in endometriotic implants?

A
  • Increased aromatase (increased E2)
  • Reduced 17BHSD activity (less conversion of E2 to E1)
  • Higher levels of ER-beta (hypomethylation in CpG islands of gene promoter)
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3
Q

Which implants have the highest level of aromatase?

A

Red implants (relative to black and cyst capsule)

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4
Q

Describe laboratory findings of OHSS

A

Hyponatremia, hyperkalemia, increased creatinine, hemoconcentration

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5
Q

What is the least likely medication to cause OHSS?

A

Recombinant LH (does not result in increased VP and VEGF)

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6
Q

Describe the benefits and evidence of efficacy of presacral neurectomy (PSN)

A
  • May be effective for the treatment of midline pain associated with menses
  • Success of the procedure depends on surgeon experience
  • long-term efficacy has not been demonstrated
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7
Q

What is LUNA used to treat and what is its efficacy?

A

Laparoscopic uterosacral nerve ablation (LUNA)

  • Used to treat pelvic pain caused by endometriosis after failed surgical management
  • Limited data suggest that LUNA is not effective
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8
Q

How does use of ICSI affect imprinting and epigenetic modifications?

A

Higher rates of genomic imprinting/epigenetic modifications (likely related to infertility > ART)

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9
Q

Name 3 disorders associated with use of ICSI

A

Beckwith-Weidemann, Angelman syndrome, and retinoblastoma

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10
Q

Does ICSI affect rate of Prader-Willi syndrome?

A

No

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11
Q

What are the best indications for use of ICSI?

A

PGD, morphology <4%, prior failed IVF despite normal semen parameters, TMS <5 million, previously frozen eggs

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12
Q

What are the indications for assisted hatching?

A

Age > 36, thick zona, prior failed IVF cycle, poor embryo morphology

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13
Q

What are positive predictors associated with pregnancy after ET?

A

US-guidance, distance from fundus, experience of MD, ease of procedure, soft catheter

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14
Q

What are negative predictors associated with pregnancy after ET?

A

Uterine contractions, blood on catheter

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15
Q

Risk factors for monozygotic twinning

A

D5 SET more monozygotic twins than D3 SET
Increased risk with AH

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16
Q

Most common adverse outcome of IVF singleton pregnancy

A

LBW (11% vs 8% in general population) vs PTD

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17
Q

What is the hardest part of creating rFSH?

A

Adding glycosylation/carbohydrates

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18
Q

What is most likely to be similar between recombinant and endogenous gonadotropins?

A

AA sequence

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19
Q

What medications are FSH only?

A

Bravelle, fertinex (menopausal urine), Gonal-F, Follistim (recombinant)

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20
Q

Name example medications of HMG (human menopausal gonadotropin)?

A

(FSH/LH): pergonal, repronex, menopur, humegon [all from menopausal urine]

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21
Q

What are required FDA labs for both partners?

A

HIV, HepBsAg, HepBcAb, HepC ab, Treponema Pall, CG/CT

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22
Q

What are required labs for egg donors?

A

HIV, Hep B, Hep C, Syphilis, GC/CT

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23
Q

What are labs required only for donor sperm?

A

HTLV, CMV IgG and IgM - different because sperm is leukocyte rich tissue

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24
Q

What is a Robertsonian translocation?

A

Occur in the five acrocentric chromosome pairs (chromosome pairs where the short arms are fairly short - 13, 14, 15, 21, and 22), and participating chromosomes break at centromeres and the long arms fuse to form a single, large chromosome with a single centromere.

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25
Q

What are the 5 acrocentric chromosomes?

A

13, 14, 15, 21 and 22

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26
Q

What proportion of RPL is idiopathic?

A

50%

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27
Q

What is the prevalence of uterine septums among patients with RPL?

A

6-7%

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28
Q

What is the prevalence of any uterine anomaly among patients with RPL?

A

10-50%

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29
Q

What is the incidence of chromosomal abnormalities in SAB?

A

50-75%

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30
Q

Describe the 3 main types of chromosomal aneuploidies seen in abortus

A
  • 90% numerical aneuploidy (trisomies, monosomies, polyploidies)
  • 10% structural abnormalities (need FISH to detect – NOT CGH)
  • Balanced translocation – 5% of RPL (usually non-homologous chromosomes)
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31
Q

What is the prevalence of Anti-phospholipid antibody syndrome among patients with RPL?

A

3-5% among RPL patients

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32
Q

What are clinical events defining APLS?

A

Need 1 or more:

  • Vascular thrombosis
  • 3 or more losses <10 weeks (issue with trophoblast invasion)
  • 1 or more loss >10 weeks (due to thrombosis)
  • PTD < 34 weeks associated with pre-ecclampsia or placental insufficiency)
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33
Q

What are laboratory findings of APLS?

A
  • Lupus Anticoagulant (LAC) – DELAYED CLOTTING in phospholipid dependent coagulation tests – (aPTT, kaolin clotting time, dilute Russell’s Viper venom [dRVVT]); this is corrected by addition of excess phospholipid but not by platelet-poor plasma)
  • Anticardiolipin antibodies (IgG or IgM) – moderate to high levels
  • High titer of antibodies to beta2 Glycoprotein 1
34
Q

How should labs be confirmed when diagnosing a patient with APLS?

A

Two separate values of same test repeated 12 weeks apart

35
Q

Can treatment of PCOS patients with metformin change their risk of RPL?

A

No

36
Q

Describe association of HgbA1c and risk of RPL among diabetic patients?

A

Directly related to A1C level

37
Q

Does subclinical hypothyroidism increase risk of RPL?

A

Yes

38
Q

What uterine anomaly is the least likely cause of RPL?

A

Arcuate
Lower risk than septum, translocation, APLS, toxic factor maternal serum

39
Q

What gene mutation is most likely to be associated with 3rd trimester loss?

A

Prothrombin mutation (not MTHFR or protein C)

40
Q

What is the risk of SAB in next pregnancy with prior miscarriage and a history of a prior liveborn?

A

0 prior miscarriages = 12 %
1 prior miscarriage = 24%
2 prior miscarriages = 26%
3 prior miscarriages = 32%
4 prior miscarriages = 26% (really, less?)
6 prior miscarriages = 53%

41
Q

What is preferred management of a patient with 3 prior losses but RPL workup is complete negative and what is the change of live birth in next pregnancy?

A

Expectant management!
Chance of live birth in next pregnancy: ~60-70%

42
Q

Does use of PGS improve outcomes for RPL patients?

A

Per Practice Committee guidelines, “available evidence currently does not support the use of PGS for patients with RPL; does not improve ongoing PR or LBR, and does not decrease SAB

43
Q

What is the risk of SAB in next pregnancy with prior miscarriage and WITHOUT a history of a prior liveborn?

A

2 or more miscarriages – 45-50%

44
Q

What can happen as a result of oocyte cryopreservation?

A

Meiotic spindle damage, ZP hardened (overcome with ICSI), cortical granule damage

45
Q

What is the preferred cryopreservative for 2PN?

A

Propanediol (propylene glycol)

46
Q

What are the advantages of extended embryo culture?

A

-Higher implantation rates
-Better synchronization
Opportunity for PGD
-Fewer multiple pregnancy rates

47
Q

What are the disadvantages of extended embryo culture?

A
  • Failure to blastulate and no transfer
  • Fewer embryos for cryopreservation possibility of no embryos for transfer (not in good prognosis patients)
  • 2-5 x increased incidence of monozygotic twinning – controversial?
  • Possibility of favoring male embryos? (males develop faster??)
48
Q

What is the most important substrate in extended media?

A

Glucose and essential AA

49
Q

Between 0 and 72 hours, what is the primary embryo energy source?

A

Lactate and pyruvate

50
Q

Between 0 and 72 hours, what is the oxygen consumption?

A

Low

51
Q

Between 0 and 72 hours, what is the AA utilization?

A

Non-essential AA

52
Q

Between 0 and 72 hours, are macromolecules required?

A

Yes

53
Q

After 96 hours through blastocyst formation, what is the primary embryo energy source?

A

Glucose

54
Q

After 96 hours through blastocyst formation, what is the oxygen consumption?

A

High, similar to active skeletal muscle

55
Q

After 96 hours through blastocyst formation, what is the AA utilization?

A

More complex essential AA

56
Q

After 96 hours through blastocyst formation, are macromolecules required?

A

Yes

57
Q

During cryopreservation, what structures freeze first?

A

polar body

58
Q

Genetic screening for sperm donors (everyone & Jewish)

A

Everyone

  • Cystic fibrosis
  • Karyotype
  • CBC, hemoglobin fractionation (thalassemias, sickle cell)
  • SMA

Jewish

  • Tay Sachs
  • Bloom syndrome
  • Canavan disease
  • Familial dysautonomia
  • Fanconi anemia
  • Gaucher disease
  • Mucolipidosis Type IV
  • Niemann-Pick disease
59
Q

Tubal obstruction: proximal vs distal

  1. % breakdown b/w the two?
  2. Causes for both?
A
  • Proximal - ⅓ - spasm, endo, TB, septic AB
  • Distal - ⅔ - GCCT / PID (risk increases w/ # of infections)
60
Q

% of false positives on HSG w/ proximal tubal obstruction?

Repeat shows one patent tube how often?

A

20-40%

repeat - 25% will have an open tube

61
Q

After HSG - fertility higher w/ oil or water-based?

A

oil

62
Q

Tubal re-anastimosis

CPR correlated w/ what?

sterilization procedure w/ best prognosis? worst?

A

Pregnancy rates correlated with length of remaining tube (≥4 cm)

Best prognosis – clips/ring/surgical (i.e. Pomeroy) (80%)

Worst prognosis – electrocautery

63
Q

Presence of hydrosalpinx:

Decreases pregnancy rate after IVF by…how much?

Increases SAB chances by…how much?

A

50%

2x

64
Q

% of women who ovulate on clomid

And what decreases chances?

A

70-80%

  • Age
  • BMI > 25
  • Severe hyperandrogenism
  • Insulin resistance
  • oligomenorrhea (amenorrhea is actually better)
65
Q

Risk of multiples w/ gonadotropin/IUI?

A

30% multiple birth

7-10% triplets or more

66
Q

IVF protocol least likely to have breakthrough ovulation

A

Gonadotropin-releasing hormone agonist stimulation protocol +/- OCP

67
Q

Fecundity rates in unexplained infertility (donor egg, IVF, gonadotropins or OI +/- IUI, TIC)

A
  • Donor egg – 50-60%
  • IVF – 25-45%
  • FSH/IUI – 15%
  • CC/IUI – 8%
  • FSH – 8%
  • CC – 5%
  • TIC and IUI (no meds) – 2-4%
68
Q

Embryo implantation rates (non-euploid by age & euploid w/ LBR)

A

non-euploid by age

  • <35 – 37%
  • 35-37 – 27%
  • 38-40 – 18%
  • 41-42 – 10%

Euploid Blastocysts & LBR:

  • excellent – 79%
  • good - 64%
  • Poor - 28%
69
Q

ICSI indications

A
  • Severe oligospermia (<5 M/mL)
  • Asthenospermia (<5% progressive motility)
  • Teratospermia (<4% normal by strict criteria)
  • Poor fertilization in prior cycles or fertilization failure
  • Polyspermy in prior cycles
  • Frozen oocytes
70
Q

Criteria for severe & critical OHSS

A

severe - Massive ascites, Hypovolemia

critical - HCT >55% (hospitalize at 45%), elevated CR w/ olgouria, VTE, impending organ failure

71
Q

Most common genetic finding in RPL?

A

Parental balanced translocation

72
Q

W/u for RPL?

A

Karyotype

APLS labs

Uterine cavity eval

73
Q

Most meaningful findings of APLS labs

A

Lupus anticoagulant & anti-cardiolipin ab’s (embryotoxic)

74
Q

Most common karyotype POC in women <35 yo

A

normal

75
Q

1, #2 and #3 most common abnormality types in POC

A
  1. autosomal trisomy (usually involving 13-16, 21 or 22)
  2. monosomy X
  3. polyploidy
76
Q

Most common singular genetic abnormality

A

Monosomy X

77
Q

If APLS, what is tx? and how effective?

A

ASA and Heparin/LMWH

LBR: 70-80% vs. ASA or nothing 20-40%

78
Q

Tx for thrombophilia?

A

Heparin (or LMWH)

79
Q

Women w/ RPL - SAB chance after FHR detected?

A

3-5x higher than normal (15-25%)

80
Q

Most common cause of familial clotting?

Risk of thrombosis if hetero? homozygous? on OCPs?

A

Factor V Leiden

Hetero - 8x increase

Homo - 80x increase

On OCPs - risk increase from 4x to 35x if hetero