Infertility Treatment

Question 1

List three indications for ICSI.

Answer 1

Failed fertilization
Very severe male factor infertility
Surgically harvested sperm

Question 2

What is assisted hatching?

Answer 2

Mechanical or chemical weakening of the zona pellucida (embryos must break through the zona pellucida/”hatch” in order to implant in the endometrium)

Question 3

List four complications of IVF.

Answer 3

OHSS
Ovarian torsion
Intra-abdominal bleeding
Infection
Multiple gestation

Question 4

What is the pathophysiology of OHSS?

Answer 4

Increased capillary permeability leads to fluid shifting from intra-vascular to extra-vascular compartments (likely mediated by VEGF)

Question 5

List five risk factors for OHSS.

Answer 5

Young age
Black race
Low body weight
PCOS
High doses of gonadotropins required
High absolute or rapidly rising estradiol
Elevated AMH
Previous OHSS

Question 6

Distinguish between preimplantation genetic diagnosis & preimplantation genetic screening.

Answer 6

PGD - preimplantation genetic testing performed when one or both parents has a known gene mutation or defect (typically one parent with autosomal dominant disorder, both parents carriers for an autosomal recessive disorder, or presence of translocation)

PGS - preimplantation aneuploidy screening performed when both parents are chromosomally normal (potential indications: RPL, AMA, recurrent implantation failure)

Question 7

What is the mechanism of action of clomiphene citrate?

Answer 7

CC is a selective estrogen receptor modulator which inhibits negative feedback of estrogen on the hypothalamus, resulting in increased gonadotropin secretion

Question 8

List four side effects of clomiphene citrate.

Answer 8

Vision changes
Headaches
Pelvic pain secondary to ovarian enlargement or ovarian cysts
PMS
Hot flashes (due to its antiestrogenic effect)

Question 9

Describe the ideal candidate for elective single embryo transfer.

Answer 9

Women 35 years or less, first or second IVF attempt, with at least 2 good-quality embryos available

Question 10

You are treating a woman with PCOS and infertility with clomiphene citrate. She tells you she has read that there has been success using metformin in combination with clomiphene citrate, and she wants to try it. How would you counsel her?

Answer 10

Reasonable in older & obese women, or those resistant to clomiphene (hyperinsulinemia increases ovarian androgen production and inhibits follicular maturation)
May increase ovulation & pregnancy rate
No evidence that live birth rate is increased

Question 11

Your patient with PCOS fails to respond to clomiphene citrate. You discuss the use of gonadotropins, but she has no drug plan and cannot afford the medications. How else might you treat her?

Answer 11

Laparoscopic ovarian drilling: use cautery or laser to create approx. 10 superficial perforations in each ovary
Comparable outcomes (pregnancy rate, spontaneous abortion, live birth rate) to gonadotropins for clomiphene-resistant women with PCOS

Question 12

What is coasting and how can it be used to decrease rates of OHSS?

Answer 12

Coasting: withholding gonadotropins while maintaining pituitary suppression with GnRH agonist or antagonist
Wait up to 3 days for estrogen levels to plateau or drop (consider cancelling cycle if no drop after 4 days, since longer coasting results in decreased pregnancy rate)
Follicles > 12 mm can still mature (they require less FSH stimulation), but small follicles undergo atresia (resulting in less VEGF production)
Results in reduced incidence OHSS without adversely affecting pregnancy rate

Question 13

You are treating a patient with a history of severe OHSS. Would you choose a GnRH agonist or antagonist for pituitary suppression? Why?

Answer 13

Antagonist - lower incidence of OHSS
When an antagonist is used for pituitary suppression, an agonist can be used to trigger endogeneous LH surge (rather than using exogeneous hCG to induce ovulation)
Endogeneous LH has a shorter half life than hCG, resulting in shorter luteotrophic stimulation and less OHSS

Question 14

What instructions would you give to a woman with OHSS who is being managed as an outpatient?

Answer 14

Use tylenol or opioids for analgesia, not NSAIDs (may compromise renal function, may interfere with implantation)
Drink 2-3 L/day to prevent hemoconcentration
No vigorous exercise or intercourse (risk of ovarian injury)
Daily weights/abdominal girth

Question 15

What therapies can you offer a woman with severe OHSS being managed as an inpatient?

Answer 15

Paracentesis (or installation of pigtail drain), culdocentesis, pleurocentesis
IV fluids - crystalloid initially, colloid if persistently intravascularly dry despite aggressive rehydration
Anticoagulation (hemoconcentration increases coagulability)

Question 16

What are the obstetric & perinatal risks associated with ART resulting in a singleton pregnancy?

Answer 16

PTB
LBW
Placental abnormalities (previa, abruption, APH, PPH)
Preeclampsia

(Trend only; evidence is far from unequivocal)

Question 17

Explain why pregnancy following frozen embryo transfer is associated with fewer LBW infants than pregnancy following fresh embryo transfer.

Answer 17

Improved endometrial environment (environment associated with production of multiple follicles may not be ideal)
Embryos which persevere through cryopreservation are likely better quality