FET

Question 1

FET Definition

Answer 1

Frozen Embryo transfer cycle is a cycle in which previously created embryos (autologous or donor) are thawed and transferred into the uterus.

Question 2

How to best prepare the uterus for future embryo transfer?

Answer 2

Utilize the natural menstrual cycle or control/manipulate environment by utilizing hormones…

Question 3

Frozen Embryo Transfer (FET)

Answer 3

goal: Create the best environment to transfer a previously frozen embryo.
considerations: Patient should have menses before starting medications for cycle
Stage embryo was frozen
Location of embryo/tissue
Protocol MD has ordered to prepare for future transfer
protocol options:
Natural/Letrozole FET
Use patient’s ovulation to time embryo transfer
Controlled FET
Suppress Natural cycle/Ovulation and control endometrial lining development and receptivity by giving exogenous hormones.

Question 4

Follicular/Proliferative phase

Answer 4

Day 1-~14 of menstrual cycle
Can be variable
Key hormones:
Follicle stimulating hormone (FSH)
Secreted from anterior pituitary
Stimulates oocyte (egg) development within the follicles
Estrogen (E2)
Secreted from follicle
High level will suppress FSH
Causes endometrial lining to develop/thicken
LuteinizingHormone (LH)
High estrogen triggers LH surge-> ovulation

Question 5

Luteal/Secretory Phase

Answer 5

Last 14 days of the menstrual cycle
Key hormones:
Progesterone (P4)
Secreted from Corpus Luteum (CL)
Causes endometrial lining to develop glands that optimize for implantation
Only elevated AFTER ovulation
Estrogen (E2)
Secreted from Corpus Luteum (CL)
Human chorionic gonadotropin (HCG)
If egg fertilized, implants
HCG->CL continues to produce E2/P4 until placenta takes over ~5-10 wks gestation

Question 6

Implantation - what day does HCG start?

Answer 6

Endometrium must be “receptive” to allow proper implantation

Implantation occurs approx 6-7+ days after ovulation

Blastocysts begin secreting hCG 7-8 days after fertilization

Question 7

FET Natural/Letrozole Priming

Answer 7

For the natural/letrozole FET protocol there may be priming with OCP

CD1 or OPK +5
OCP 7-231 days:

OCPs taken per current phase of cycle*:
Ensure patient take 1 pill daily, active pills NOT placebo:
If started early follicular (CD 1-3): 10-15 days
If started late follicular (CD 4-ovulation): 14-21 days
If started luteal (LH+5): 7-10 days

baseline - 3-5 days later:
3-5 days after stopping the birth control pill the patient will get their full flow period. They will need their baseline ultrasound during this time – ideally 4 days after last dose however avoid weekend/holidays

Answer 8

baseline w/ menses - CD1-4:
Patient tocontact withCD1,bring in forBaseline USCD 1-4 to determine if anyovarian cysts presentthat could impactresponse/outcomeLMP is the date of
first day of full flow period
monitoring:
Monitoring will include ultrasounds tracking follicular growth and lining thickness and bloodwork including E2, LH & P4 as requested by the provider
Monitoring:
1. Cycle Day 9-11 for first US & potential bloodwork
Then continued until ovulation is confirmed or triggered
Once ovulation has been confirmed or triggered then you will be able to establish all other medication instructions and the transfer date

Question 9

FET: Letrozole

Answer 9

baseline w/ menses
ltz start cd2-4 for 5 days:

Letrozole will be started on cycle day 2-4 and continue for five days. If dose not specified then assume 5 mg (2 tablets)
LMP is the date of
first day of full flow period
monitoring: Monitoring will include ultrasounds tracking follicular growth and lining thickness and bloodwork including E2, LH & P4 as requested by the provider
Cycle Day 9-11 for first US & potential bloodwork

Once ovulation has been confirmed or triggered then you will be able to establish all other medication instructions and the transfer date

Question 10

Once ovulation has been confirmed or triggered then you will be able to establish all other medication instructions and the transfer date

Answer 10

In a natural cycle, after the egg ovulates from its follicle, that follicle will become a hormone secreting structure called Corpus Luteum(CL). It will begin secreting progesterone and estrogen. However, after a few days this structure will begin to degenerate and stop hormone production unless there is HCG.
If that month there is embryo implantation then the placenta will begin producing HCG therefore keeping the corpus luteum active and producing progesterone and estrogen to support the early pregnancyOvidrel is commonly given to trigger ovulation to ensure proper timing for FET.
If a patient has an LH surge, Ovidrel may be given as a “booster” to stimulate the corpus luteum to continue producing progesterone and estrogen.
(Ovidrel=HCG which is the hormone of pregnancy)
Often supplementation with exogenous (external) P4 is not required.

Question 11

FET bloodwork

Answer 11

Throughout Natural/Letrozole FET cycles bloodwork will be monitored to assess when ovulation occurs. We will primarily be tracking the rise of E2 leading into ovulation, the quick surge of LH the day before ovulation and the rise of P4 following ovulation
Progesterone levels are checked 2 days after ovulation (LD2) to ensure a proper rise.
The ideal range is >9, in this case no supplementation will be needed.
If <2we are concerned and this could result in cycle cancellation or delay of transfer. See FET 02 for details
If >2 but <9we will supplement with progesterone starting the AM of LD3(Endometrin/Prometrium TID or Crinone8% QD) and continue until pregnancy test

Question 12

FET: Natural/letrozole

Answer 12

FET: Natural/letrozole
LDO is the day of ovulation
Transfer Date is dependent on the day the embryo was frozen:
Day 3 Embryos transferred on LD 3 (3 days after ovulation)
Blastocyst Embryos transferred on LD 5 (5 days after ovulation)
Medrol: Option to waive, per provider
Valium will be taken one hour before transfer to help with uterine relaxation
Progesterone level is check on LD2
If P4 >9, no supplementation is need
If P4 2.0-9: Begin vaginal P4 (PV) the AM of LD3 and continue until pregnancy test.
If P4 < 2, add HCG level to blood draw to confirm adequate booster/trigger–then follow provider order
Options: Cancel FET or begin P4 (IM or PV) and push date of FET

Question 13

Ovidrel Booster—Ideas documentation

Answer 13

If Ovidrel is used to Booster to thenatural LH surge, you must document in the cycle summary ADD-> Booster DO NOT list as a Trigger
Edit treatment plan:
Add drug->Booster-Ovidrel
Confirm the Ovidrel
Enter the LH surge into Treatment plan to set LD0
LD0 should be day following LH surge

Question 14

Medrol (Methylprednisolone)*

Answer 14

16 mg tablet
Sig: 1 pill PO once daily x 5 days
Quantity: 5 tablets, no refill
*NYC will d/c using ~10/2023

Question 15

Valium (Diazepam)

Answer 15

10 mg tablets
Sig: 1 pill one hour prior to procedure the second is an optional dose 6-8 hours later
Quantity: 2 tablets, no refill

Question 16

If LD2 bloodtest indicates need for P4 supplementation order one of the following options

Answer 16

ProgesteroneVaginal options:
Endometrin 100 mg vaginal insert tablets or
Prometrium 200mg tablets
Sig: 1 tablet three times daily vaginally for 16 days
Quantity: 50 tablets, 3 refills
OR
Progesterone in oil (sesame, ethyl oleate-compounded)
Sig. Inject 1 ml IM once daily (dose will titrate per instructions)
Quantity: 3 vials, 3 refills
Will also need supplies(syringes/needles)

Question 17

ovidrel

Answer 17

250 mcg prefilled syringe
Sig: Inject SQ full dose once when specified
Quantity: 1 syringe

Question 18

Controlled FET

Answer 18

Medications are given to prepare the uterus for embryo transfer:
BCPs and Lupron can be given to gain control and suppress hormonal activity
Estrogen is given to thicken the uterine lining
Progesterone is started when indicated, after Endometrium is developed,

Question 19

Controlled FET pros/cons

Answer 19

Candidate
Any patient that can tolerate SQ/IM injections

Pros
Less monitoring
Can determine target date for transfer based onprotocol and expected response
No risk of natural conception, since no ovulation
Cons
Multiple weeks of injections
Estrogen /PIOcontinues until 9 & 12wksgestation respectively

Question 20

FET: Controlled-Estrace

(loop in the estrace for 7 days)

Answer 20

OCPs can be started in the follicular phase (CD1-3) or in the luteal phase (five days after positive OPK). OCPs will be continued for 14-28 days, active pills ONLY no placebo.For the last 7 days of OCP the patient will need to overlap with Lupron injections 10 IU SQ daily. These injections will be continued until progesterone injections are started
LMP is the date of Estradiol start

3-5 days after stopping the birth control pill the patient will get their full flow period. They will need their baseline ultrasound during this time – ideally 4 days after last dose however avoid weekend/holidays

With menses after the baseline appointment the patient will be instructed to start
estrace/estradiol 2mgtablets orally. They will follow the scheduled below.

lupron inections started last 7 days of OCP and continued

Estradiol 2mg dosing Schedule:
1 tablet (2mg/day) orally for 6 days, then
Increase to 1 tablet twice daily (total 4 mg/day) for 3 days, then
Increase to 2 tablets twice daily (total 8mg/day) until Progesterone start
On day of progesterone start, decrease to 3 tablet for 3 days
(i.e. 2 tabs AM and 1 tab PM- total 6 mg/day), then
Decrease to 1 twice daily (4mg/day) thereafter until bHCG.
If positive, continue 1 twice daily until 8w6d gestation.
An ultrasound appointment will be scheduled after 12-15 days on the estradiol tabletsto check lining

Question 21

FET: Controlled- vivelle

(Vivien is 1, 1, 2, 4)

Answer 21

OCPs can be started in the follicular phase (CD1-4) or in the luteal phase (five days after positive OPK). OCPs will be continued for 14-28 days.
For the last 7 days of OCP the patient will need to overlap with Lupron injections 10 IU SQ daily. These injections will be continued until progesterone injections are started

LMP is the date of Vivelle patches start

Estrace pills can be used instead of patches. 1 x 2 mg PO tablet = 1 x patch

lupron inections started last 7 days of OCP and continued

3-5 days after stopping the birth control pill the patient will get their full flow period. They will need their baseline ultrasound during this time – ideally 4 days after last dose however avoid weekend/holidays

With menses after the baseline appointment the patient will be instructed to start Vivelle patches placed on their lower abdomen and/or back. They will follow the scheduled below.
Vivelle Patch Schedule:
With menses place 1 patch for 72 hrs
Remove and replace with 1 patch for 72 hrs
Remove and replace with 2 patches for 72 hours
Remove and replace with 4 patches for 72 hours
Continue at 4 every 72 hrs until instructed otherwise
An ultrasound appointment will be scheduled after 12-15 days on the patches to check lining

Question 22

lining check - what date do you need to start progesterone by?

(progy at 17)

Answer 22

needs to be 7 mm, If the lining is within the ideal range the provider will confirm the progesterone injections start date. With this date you will be able to establish all other medication instructions and the transfer date.

If not yet at the ideal thickness the provider will considered additional estrogen supplementation such as Estrace tablets PO or PV or Estradiol Valerate IM and return for another check in 2-4 days.

Progesterone should be started no later than CD17

Question 23

IM Progesterone Teaching

Answer 23

Draw up with a 18, 20 or 21 gauge 1½ inch needle.
Then switch to a 22 gauge 1½ inch needle for injection if Sesame/Olive Oil
OR a 25 gauge 1½ inch needle if Ethyl Oleate

Best positions for administration is leaning against a table or chair. If self-administration lean again a wall or back of a chair and shift body to one side.

Important tips for pain relief:
Warm up the oil slightly to body temperature by holding it in hand or placing a warm cloth around the vial
Deep tissue massage immediately after and get up and walk around
Apply heating pad or compress to site after injection

Question 24

FET: Controlled (continued)

Answer 24

Lupron will stop once IM P4 is started
Transfer Date is dependent on the day the embryo was frozen:
Day 3 Embryos transferred on LD 3 (on the 5th day of IM P4)
Blastocyst Embryos transferred on LD 4 (on the 6th day of IM P4)
Vivelle patches continue 2 patches every 72 hrs until pregnancy test. If pregnant will continue until ~9 weeks gestation

Prog continue at 1.5mL until pregnancy test. If pregnant will continue prog. until ~12 wks gestation (dosage will decrease to 1ml at 7wks)*

Question 25

Controlled FET Protocol

Answer 25

Suppression/priming (CD 1-4 or 5 days after +OPK) 14-28 days:Beginluprondaily injection (10 units) last 7 days of OCPs (best to use longer course of pills to avoid flare effect).
Lupron continue daily until P4 injectionbegins

Baseline 3-5 days after d/c of BCP (avoid weekend/holiday)Ensure period has started before starting Vivelle patch..
Vivelle patch q 3 days—1, 1, 2, 4,cont4 q3day until day of P4 start. Day of P4 start change to 3 patches, in 3 days decrease to 2 patches and stay on 2 until 9wks gest.
Lining Check U/S ~12-15 days aftervivellestart (Must be before D17): If EM >7mm, MD will advise when to begin PIO, day of PIO start d/clupron
PIO is daily titrated up in the following doses (50mg/ml PIO)
½ ml, ½ ml , 1ml, 1ml, 1ml, 1.5ml–stay on 1.5 until pregnancy test. If positive, will continue at this dose until 7weeks, then decreased to 1ml until 12 weeks.
Can switch to vaginal at 8 6/7th wks gest.
Blast transfer will be day 6 of PIO (LD4)

Question 26

FET Controlled Medications - OCP

(eclipse the OCP)

Answer 26

Reclipsen 0.15-0.03 mg tablets
Sig: 1 pill daily for X days (14-28 unless specified)
Quantity: 28 pill as it is always dispensed in pack, refills 3

Question 27

FET controlled meds - Estrogen

Answer 27

Vivelle Patch 0.1 mg 24 hr patch
Sig: 1-4 patches (as instructed) q72h, until instructed otherwise
Quantity: 32 patchs, 3 refills
OR
Estrace (Estradiol tablets) 2mg #60 w/refills
Sig: Take orally as directed

Question 28

FET controlled meds - progesterone

Answer 28

Progesterone in Oil (Sesame, Olive or Ethyl Oleate)
Progesterone in Oil 50 mg/mL, 10 mL vials
Sig: Inject 1 mL (dose will titrate up per instructions) IM once daily
Quantity: 3 vials, 3 refills

Question 29

FET controlled meds - lupron

Answer 29

(Leuprolide Acetate)
Sig: Inject SQ 10 IU daily
Quantity: 1 kit/vial, refills 3

Lupron is specialty. If self pay send to Alto, order compounded 4-wk kit (28 vials). If insurance send to preferred specialty 2-week kit 1mg/0.2mL

Question 30

FET controlled meds - medrol
(meddie is 16)

Answer 30

Methylprednisolone) 16 mg tablet
Sig: 1 pill PO once daily x 5 days
Quantity: 5 tablets, no refill
*NYC to d/c use ~ 10/2023

Question 31

FET controlled meds - valium

Answer 31

Diazepam) 10 mg tablets
Sig: 1 pill one hour prior to procedure the second is an optional dose 6-8 hours later
Quantity: 2 tablets, no refill

Question 32

all meds except

Answer 32

expect Lupron, can be filled through local or specialty pharmacy

Question 33

Notes

Answer 33

If patient does not follow instructions:
i.e. Did not take trigger on assigned date or begin PIO as instructed—Transfer day will need to be moved!
Natural/Let FET, once triggered, does not need a repeat US unless MD had a concern
LH surge may be interpreted differently , per provider
LH>20 , should indicate an LH surge however this is also dependent on US, E2, etc..And hormone analyzer running the test.
Analyzer at Spring is very sensitive andLH>12 may indicate a LH surge..
Check in with your provider /team
May compare results over multiple days to determine LH surge day and advise best day for transfer day

Question 34

The two week wait

Answer 34

The hormonal symptoms for the medications following the transfer will make them feel as though they are about to get their period and/or are pregnant. It is therefore important to remind them to try and not read into these symptoms

Recommendations during this time include:
Take it easy the first 1-3 days, no bed rest but avoid strenuous activity and high stress. After this okay to resume all normal activity. Exercise is okay but no lifting over 30 lbs and avoid bearing down in abdomen.
No hot tubs, saunas or hot yoga
Normal diet and fluid intake – following standard pregnancy precautions (no alcohol, moderate caffeine (1-2 8 oz cups daily) raw animal products, unpasteurized cheese/milk, processed deli meats, fish high in mercury)
No intercourse/orgasm at minimum for one week, however most patient opt to wait until the pregnancy test
Due to false readings we do not recommend checking home urine pregnancy tests during this time!

Question 35

Progyny Patients-Multiple Embryo Transfer (MET) policy

Answer 35

Progyny patients desiring Multiple Embryo Transfers (MET) - require pre-approval
Progyny patients require pre-approval for multiple embryo transfers before starting thecycle, and only those that adhere to ASRM guidelines will be covered by insurance.
If denied, the patient could still plan to proceed with plan it will just not be covered by Progyny.

This process will mostly be handled by Finance Team, but will require RNs or PNs sendingthe Order to Finance beforetreatment in which a MET is desired .

Utilize the @ phrase @METforProgyny in remarks of order to Finance-Progyny to generate the paragraph template, and fill in the required information (cycle type, number of embryos to transfer, stage of embryos)

Question 36

eset

Answer 36

elective single embryo transfer (this always means just one)

Question 37

when do we check P4?

(P on day 2)

Answer 37

luteal day 2, EVEN IF IT’S ON THE WEEKEND

Question 38

crinone

Answer 38

use in the am, the heat and friction help w/ absorption

Question 39

when to start progesterone?

(progy transferred at 3)

Answer 39

transfer day 3

Question 40

Progesterone lower than expected following ovulation…

Answer 40

if P4 is less than 2 = Provider to advise
Cancellation vs. Supplementation and move transfer date

Progesterone in oil (IM)
vaginal P4

New Transfer date will be on NEW LD3 (D3) or LD4 (Blast) -Start of PIO = LD-1 (LD minus 1) or Start of PV= LD0

Question 41

P4

Answer 41

look at this slide - start at .25 (check this)

Question 42

after starting E2, how long until you start progesterone?

Answer 42

usually around day 17 is good, but it depends on how thick the lining is

Question 43

FET - when is LDO?

Answer 43

the start of progesterone determines LD0 and future transfer date.