Endometrial Preparation for Frozen Embryo Transfer (FET) Zitao Liu, MD, PhD New Hope Fertility Center, NY

Endometrial Preparation for Frozen Embryo Transfer (FET) Zitao Liu, MD, PhD New Hope Fertility Center, NY

Natural Cycle

FET Protocol for endometrial preparation N FET, including modified N FET HRT FET: Estrogen, Progesterone

Priming Estrogen in HRT FET 0.75 mg of micronized estradiol (oral administration) 1.25 g of estradiol gel (transdermal administration) 1 mg of estradiol valerate (oral or vaginal administration).

HRT FET: Effect of Duration of Estradiol Priming (Donor Oocyte): I Conclusions: Endometrial receptivity: a wide duration of E2 treatment (until 2 months), Breakthrough bleeding: >40 day: 7.2% SAB: 10 d, significant higher The best results: 11 to about 40 days. Borini A et al. Effect of duration of estradiol replacement on the outcome of oocyte donation. J Assist Reprod Genet. 2001 Apr;18(4):185-90.

HRT FET: Effect of Duration of Estradiol Priming (Donor Oocyte): II Endometrial preparation, estrogen therapy lasting more than 7 wk is associated with reduced PR and IR (P = 0.01 and P = 0.02, respectively). Soares SR et al., Age and uterine receptiveness: predicting the outcome of oocyte donation cycles. J Clin Endocrinol Metab 2005;90:4399 4404

Weissman A et al., What is the preferred method for timing natural cycle frozen-thawed embryo transfer? Reprod Biomed Online 2009;19:66 71 N FET vs modified N FET Criteria for ovulation detection included: (i) fall in serum oestradiol concentration compared with the previous test; (ii) rise in serum progesterone concentration >1.5 ng/ml; and (iii) disappearance or typical change in the shape of the lead follicle. Criteria for HCG administration included: (i) visualization of a leading follicle >17 mm in diameter by TVS; (ii) serum oestradiol concentration >150 pg/ml; and (iii) serum progesterone concentration <1 ng/ml

GnRH agonist to prevent ovulation in FET Glujovsky D, et al., Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes. Cochrane Database Syst Rev 2010;1:art. no. CD006359.

Elevated Progesterone before trigger in N FET (I) Modified N FET (hcg trigger): blastocyst transfer, no luteal phase support Groenewoud ER et al., The effect of elevated progesterone levels before HCG triggering in modified natural cycle frozen-thawed embryo transfer cycles. Reprod Biomed Online 2017;34:546 554

Elevated Progesterone before trigger in N FET (II) Modified N FET (hcg trigger): blastocyst transfer, no luteal phase support Groenewoud ER et al., The effect of elevated progesterone levels before HCG triggering in modified natural cycle frozen-thawed embryo transfer cycles. Reprod Biomed Online 2017;34:546 554

Elevated Progesterone before trigger in N FET (III) Modified N FET (hcg trigger): blastocyst transfer, no luteal phase support Groenewoud ER et al., The effect of elevated progesterone levels before HCG triggering in modified natural cycle frozen-thawed embryo transfer cycles. Reprod Biomed Online 2017;34:546 554

hcg supplement with progesterone supplement in FET 250 unit of hcg at progesterone initial supplement Ben-Meir A et al., The benefit of human chorionic gonadotropin supplementation throughout the secretory phase of frozen-thawed embryo transfer cycles. Fertil Steril 2010;93:351 354

Endometrial Thickness in FET Clinical Pregnancy HRT FET El-Toukhy T et al., The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles. Fertil Steril 2008;89:832 839

Luteal Phase Support in FET : Progesterone: Vaginal Cream vs IM (I) day 3 FET with luteal support using 25 50 mg/d IMP or 8% Crinone twice daily Kaser DJ et al., Intramuscular progesterone versus 8% Crinone vaginal gel for luteal phase support for day 3 cryopreserved embryo transfer. Fertil Steril 2012;98:1464 1469

Luteal Phase Support in FET : Progesterone: Vaginal Cream vs IM (II) Blastocyst transfer after Crinone 8% (90 mg twice a day) or IMP (50 mg once daily): started on Day 15 of estrogen therapy Shapiro DB et al., Progesterone replacement with vaginal gel versus i.m. injection: cycle and pregnancy outcomes in IVF patients receiving vitrified blastocysts. Hum Reprod 204;29:1706 1711

Luteal phase support in ET: oral vs pv progesterone oral dydrogesterone 30 mg daily (10mg TID) vs micronized vaginal progesterone (MVP) 600 mg daily (200mg TID) (Phase III) Progesterone start at the date of OPU Tournaye H et al., A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral ydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization. Hum Reprod 2017; 32:1019 1027

HRT FET: Progesterone level (I) Serum progesterone at the date of blastocyst transfer: intramuscular (IM) P4 at a constant 50 or 75 mg per day Kofinas JD et al., Serum progesterone levels greater than 20 ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates. J Assist Reprod Genet 2015;32:1395 1399

HRT FET: Progesterone level (II) Blastocyst FET after vaginal progesterone pessary: Progesterone level: 2-3 days after FET Yovich JL et al., Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement. Reprod Biomed Online 2015;31:180 191

HRT FET vs N FET Groenewoud ER et al. A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer. Hum Reprod 2016;31:1483 1492

HRT FET: timing Clinical practice proposal for embryo transfer timing in the different preparation methods. tor, theoretical oocyte retrieval, E2, estradiol, P, progesterone, NC, natural cycle. Maken S et al., embryo transfer: a review on the optimal endometrial preparation and timing Hum Reprod. 2017;32(11):2234-2242.

N FET: timing Clinical practice proposal for embryo transfer timing in the different preparation methods. tor, theoretical oocyte retrieval, E2, estradiol, P, progesterone, NC, natural cycle. Maken S et al., embryo transfer: a review on the optimal endometrial preparation and timing Hum Reprod. 2017;32(11):2234-2242.

Endometrial Receptivity: transcriptomic signature (134 selected genes) Díaz-Gimeno P et al., A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertil Steril 2011;95:50 60

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