P-640 Impact of adding oral dydrogesterone (OD) in patients with low serum progesterone (P) levels in artificially prepared frozen embryo transfer cycles (FET-HRT)
Authors: Pais F , Mackens S , Roelens C , Amghizar S , Van Landuyt L , De Vos M , Tournaye H , Drakopoulos P , Blockeel C 
Published: June 2022

Study question

In case of low serum P on the day of FET (PFET), does the addition of OD to micronized vaginal progesterone (MVP) normalise reproductive outcomes?

Summary answer

In case of low serum PFET, adding OD results in ongoing pregnancy rates (OPR) comparable to those of patients who had normal serum PFET.

What is known already

Low serum PFET is associated with increased rates of early pregnancy loss (EPL) and reduced live birth rates in FET HRT cycles. While adding subcutaneous P injections to vaginal progesterone has been shown to normalize clinical outcomes in case of low serum PFET, it is unknown whether adding OD has a similar effect.

Study design, size, duration

This is a retrospective, single-centre cohort study in a tertiary IVF-clinic. 694 unique patients who had a single blastocyst transfer in an HRT cycle were included. As soon as an endometrial thickness of ≥ 6.5mm was reached following estradiol valerate priming, MVP (400mg,twice daily) was started, followed by FET on the 6thday of MVP. All patients underwent serum P measurement just prior to FET. Serum PFET was analysed using a validated electrochemiluminescence immunoassay (Cobas 6000®,Roche).

Participants/materials, setting, methods

Clinical outcomes of patients with normal serum PFET(≥8,8ng/dl) following the routine MVPsupplementation were compared with those of patients with low serum PFET(&lt;8,8ng/dl) in whom OD(30mg TID) was added from FET onwards. Primary outcome was OPR, defined as a vital intra-uterine pregnancy at 8 weeks. EPL was defined as biochemical pregnancy loss or early miscarriage. A multivariate regression model was developed adjusting for age, BMI, endometrial thickness, embryo quality and estradiol level.

Main results and the role of chance

Mean age in the MVP-only versus the MVP+OD group was 34.6(±4.2) and 33.6(±4.3) years, respectively (p = 0.01). No other statistically significant differences were seen among both groups for BMI, endometrial thickness nor embryo quality. A normal serum PFET level was observed in 547/694 (78.8%) of patients, who continued MVP as planned, whereas a low serum PFET level was detected in 147/694 (21.2%) patients who received additional OD supplementation next to MVP from the day following FET onwards. The mean serum PFET level was 14.6 (±5.8) ng/ml in the MVP-only group and 7.0(±1.8) ng/ml in the MVP+OD group. The OPR was comparable between both groups: 40.8% for MVP only versus 40.0% for MVP+OD (p = 0.86). The biochemical pregnancy rates were 55.0% and 60.5% (p = 0.23) and the EPL rates were 14.4% and 21.1% (p = 0.05) in the MVP-only group vs. the MVP+OD group, respectively. Multivariate logistic regression analysis indicated that OPR was not associated with the investigated approaches (OR 0.92, SD 0.18, CI 0.63-1.35, p = 0.68). Only embryo quality was significantly associated with OPR (OR 3.03, SD 1.11, CI 1.48-6.21, p = 0.002).

Limitations, reasons for caution

The main limitation is the retrospective nature of this study with the risk of unmeasured confounder bias. While OPR is a less robust outcome parameter compared to LBR, LBR data will be presented once available.

Wider implications of the findings

Additional OD supplementation in patients with low P gives rise to comparable OPRs as observed in patients with normal P. Prospective studies are required to identify the individualized luteal phase support strategy that combines optimal LBR and low EPL rates.

Trial registration number

Not Applicable