P-653 Natural proliferative phase frozen embryo transfers: a novel, safe and efficient transfer strategy
Authors: Santana C , Mascarós Martinez J M , Neves A R , Semenova T , Nunes S G , Reis Soares S , Santos-Ribeiro S 
Published: June 2023

Study question

How do natural proliferative phase for frozen embryo transfers (NPP-FET) compare to traditional artificial and natural cycle FETs in terms of pregnancy and neonatal outcomes?

Summary answer

NPP-FETs were associated with similar ongoing pregnancy rates after 22 weeks, but with less miscarriage rates comparing to artificial cycles.

What is known already

The best FET protocol for endometrial preparation is still controversial. A natural cycle (NC) FET may require more visits to the clinic and provides less flexibility. Conversely, artificial cycles (AC), although being more flexible in terms of scheduling, have been previously associated with higher rates of miscarriage and maternal morbidity. Here we describe an alternative FET strategy (NPP-FET) in which, during an unmediated ovulatory cycle, progesterone is initiated as soon as the endometrium proliferation reaches 7 mm of thickness, regardless of the size of the dominant follicle and without the administration of exogenous hCG or spontaneous LH peak.

Study design, size, duration

We performed a single center retrospective cohort study of FET cycles performed between January 2020 and June 2022 (n = 2158). Only single embryo blastocyst stage transfers were included. The main outcome was ongoing pregnancy rate after 22 weeks. Secondary outcomes included the number of visits to the clinic during monitoring, serum levels of progesterone on the day of FET, livebirth (LBR) and miscarriage rates, and maternal/perinatal outcomes.

Participants/materials, setting, methods

FETs cycles were divided in three subgroups: NC, NPP and AC. For the main outcome measures, a multivariable logistic regression was performed, to adjust for potential confounding (oocyte age/source, use of PGT-A and embryo quality), followed by pairwise comparisons whenever statistically significant.

Main results and the role of chance

In total, 2158 FET cycles were analysed (1219 NC, 277 NPP and 662 AC). The mean number of visits before FET planning were 2.14, 1.83 and 1.33 for NC, NPP and AC FETs, respectively (p &lt; 001 for all pairwise comparisons). Mean progesterone levels on the day of transfer were significantly higher after NPP and NC (29.4 ng/mL and 40.2ng/mL, respectively), compared to AC (12.7 ng/mL). Progesterone rescue therapy (administered whenever serum progesterone &lt;8.8 ng/mL) was also significantly more frequently needed following AC (24,9% for AC versus 0.6% and 2.6% in NC and NPP, respectively). The ongoing pregnancy rates after 22 weeks were 57.3% for NC, 55.6% for NPP and 54.5% for AC. LBRs following NPP were comparable with NC (38.9% and 42.7%, respectively), and significantly lower with AC (36.0%) compared to NC. The miscarriage rates were significantly lower after NPP and NC-FET when compared to AC (18.4%, 24.3% and 30.7% respectively). Considering maternal outcomes, NPP and NC were associated with a significantly lower risk of first trimester bleeding compared to AC (17.5%, 13.8% and 36.7%, respectively). The rate of gestational hypertensive disorders did not vary significantly (7.5% for NPP, 9.9% for NC and 12.6% for AC).

Limitations, reasons for caution

While serum progesterone and miscarriage rates comparable to NC-FET allude to the possibility that ovulation may still occur in NPP-FETs, this study cannot establish such causality due to its retrospective design. Moreover, the study may have been underpowered to detect clinically relevant subgroup differences such as for hypertensive disorders.

Wider implications of the findings

NPP-FETs seems to be an effective and safe alternative, potentially wielding both the advantages of the natural proliferative endometrium of the NC with the ease for scheduling of ACs. Nonetheless, further investigation is warranted attempting also to confirm whether ovulation does indeed still occur despite the progesterone administration.

Trial registration number

not applicable