How to proceed with FET cycle with 4mm endometrial thickness and follicles on Progynova (Estradiol) 2mg bd?

Management of FET Cycle with Thin Endometrium on Progynova

Increase the estradiol dose immediately by adding vaginal Femoston (estradiol/dydrogesterone) to the current oral Progynova regimen, continue monitoring endometrial development, and proceed with transfer once endometrial thickness reaches ≥7 mm. 1

Immediate Management Steps

Optimize Estrogen Delivery

• Add vaginal Femoston to the current oral Progynova 2mg BD regimen rather than canceling the cycle, as this combination approach has demonstrated improved endometrial receptivity and clinical outcomes in patients with inadequate endometrial response 1

• The vaginal route provides direct endometrial exposure and may overcome poor oral absorption or first-pass metabolism that limits endometrial response 2

• Continue current oral Progynova 2mg BD while adding vaginal estradiol supplementation 1

Address the Follicular Development

• Suppress the developing follicles with GnRH antagonist to prevent premature ovulation and maintain cycle control, as GnRH antagonist cycles probably improve clinical pregnancy rates compared to agonist protocols (OR 0.62,95% CI 0.42 to 0.90) 3

• The 15mm follicle poses risk of spontaneous ovulation which would disrupt the programmed cycle timing 3

• GnRH antagonist allows continuation of the artificial cycle without converting to a natural cycle protocol 3

Monitoring and Decision Points

Endometrial Thickness Targets

• Target minimum endometrial thickness of 7 mm before proceeding with progesterone administration and embryo transfer 1

• Clinical pregnancy rates improve with increasing endometrial thickness, though transfers can proceed with thickness as low as 5-7 mm with appropriate counseling 2, 1

• In one case report, successful twin pregnancy was achieved with 7.6mm endometrium after transdermal therapy augmentation in a patient whose initial thickness was only 5.0mm 2

• Patients with endometrial thickness <7mm who received Progynova plus Femoston had higher clinical pregnancy rates (52.9%), embryo implantation rates (35.8%), and live birth rates compared to those receiving Progynova alone with similar thin endometrium 1

Estradiol Level Considerations

• Do not base the decision to proceed solely on estradiol levels, as maximum E2 levels do not significantly correlate with clinical outcomes when adequate endometrial thickness is achieved 1

• The focus should remain on endometrial thickness rather than serum estradiol concentration 1

Progesterone Initiation Protocol

Timing and Dosing

• Begin progesterone supplementation only after achieving target endometrial thickness of ≥7 mm 4, 1

• Use vaginal progesterone 800 mg/day for luteal phase support in artificial FET cycles, as this dose improves reproductive outcomes compared to 600 mg/day (higher hCG positive rates and ongoing pregnancy rates) 5

• In artificial cycles, progesterone supplementation begins on the day of endometrial transformation 4

Duration of Support

• Continue estrogen and progesterone at original doses for 3-4 weeks after positive pregnancy test, then gradually reduce dosage to complete discontinuation within 2 weeks 4

• This extended support is critical in artificial cycles where no corpus luteum exists to provide endogenous hormone production 4

Common Pitfalls to Avoid

Do Not Cancel Prematurely

• Avoid canceling the cycle at 4mm thickness on day 8 - this is premature, as augmentation with vaginal estradiol can salvage the cycle 1

• Historical practice of canceling cycles with thin endometrium has been superseded by evidence supporting combination estrogen therapy 1

Do Not Ignore Follicular Activity

• Do not proceed without addressing the 15mm follicle, as spontaneous ovulation will desynchronize the artificial cycle and compromise outcomes 3

• Failure to suppress follicular development may necessitate conversion to a natural cycle protocol, which requires different progesterone timing 3

Do Not Use Inadequate Progesterone Dosing

• Avoid using progesterone doses <800 mg/day vaginally in artificial cycles without GnRH analogue pre-treatment, as lower doses (600 mg/day) result in inferior outcomes 5

• Inadequate progesterone dosing is a common cause of implantation failure in artificial FET cycles 5

Alternative Consideration

If endometrial thickness fails to improve after 3-5 additional days of combination oral plus vaginal estradiol therapy, consider cycle cancellation and conversion to a stimulated or natural cycle protocol in the subsequent attempt, as stimulated cycles may improve clinical pregnancy rates compared to programmed cycles (OR 1.63,95% CI 1.12 to 2.38) 3