Frozen Embryo Transfer Protocol Comparison

We need standardized terminology for frozen embryo transfer (FET) protocols to compare them. There are many permutations of FET protocols which makes comparing them challenging. For this reason, the following standard protocols are being defined and numbered.

META IVF Standard FET Protocol List Version 1.0

Often all estradiol and progesterone is continued until 12 weeks then stopped without taper. Acceptable alternatives include stopping estradiol and progesterone anywhere between 9 weeks 0 days and 12 weeks 0 days gestation or tapering during this timeframe.

Total Natural FET

FET Protocol #1: Total Natural FET (no medications, only monitoring US and labwork).

1A Home urine LH monitoring with TVUS and labs (estradiol, progesterone, and LH) on cycle day 10-12.

1B Check labs (estradiol, progesterone, and LH) 2-4 days after LH surge on home urine LH monitoring. No in office US monitoring.

1C Home urine LH monitoring only, no in office monitoring.

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Modified Natural FET

FET Protocol #2: Unstimulated Modified Natural FET (HCG trigger, vaginal progesterone daily after ovulation).

2A HCG trigger, vaginal progesterone daily after ovulation

2B HCG trigger only, no vaginal progesterone

2C no HCG trigger, vaginal progesterone only

FET Protocol #3: Gonadotropin Stimulated Modified Natural FET (HCG trigger, vaginal progesterone daily after ovulation).

FET Protocol #4: Letrozole Stimulated Modified Natural FET (HCG trigger, vaginal progesterone daily after ovulation).

FET Protocol #5: Modified Natural FET after transvaginal oocyte retrieval (typically used when transferring a euploid embryo from a previous cycle after an oocyte retrieval).

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Artificial Hormone Replacement Therapy (no corpus luteum formation)

Vaginal estradiol 2mg daily or BID can be added in from the start or if the lining is thin on initial TVUS. Typically 10-14 days of oral estradiol are used before TVUS is performed to evaluate the endometrium. Target endometrial lining of 6.0mm or greater (7.0mm preferred) and a trilaminar appearance is generally considered acceptable to proceed with progesterone start and embryo transfer. Typically estradiol and progesterone are measuring on the day of TVUS. Estradiol of > 80 pg/mL and progesterone of < 1.0 ng/mL are generally considered appropriate to proceed with the progesterone start and embryo transfer.

For anovulatory women (such as menopause, PCOS, or anovulation) a withdrawal bleed is preferred. However, estradiol can also be started randomly. Withdrawal bleed is preferred with a physiological approach of estradiol 2mg PO BID x 20 days with the addition of 400mg micronized progesterone PO x 10 days added to the last 10 days of estradiol. An acceptable alternative is oral contraceptive pills (OCPs) for 14 days. In some anovulatory women with thin endometrium 14 days of OCPs will not cause a withdrawal bleed.

FET Protocol #6: Artificial Hormone Replacement Therapy (estradiol 2mg PO TID, vaginal micronized progesterone 200mg TID).

FET Protocol #7: Artificial Hormone Replacement Therapy (estradiol 2mg PO TID, vaginal micronized progesterone 200mg four times per day).

FET Protocol #8: Artificial Hormone Replacement Therapy (estradiol 2mg PO TID, vaginal micronized progesterone 200mg TID and progesterone in oil 50mg IM every 3 days).

FET Protocol #9: Artificial Hormone Replacement Therapy (estradiol 2mg PO TID, progesterone in oil 100mg IM daily).

FET Protocol #10: Artificial Hormone Replacement Therapy (estradiol 2mg PO TID, progesterone in oil 50mg IM daily).

FET Protocol #11: Artificial Hormone Replacement Therapy (estradiol 2mg PO TID, progesterone in oil 100mg IM daily and vaginal micronized progesterone 200mg BID).

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Euploid Embryo Outcomes by Age at Oocyte Retrieval and Embryo Day