P-672 Is there a sweet spot for follicular size and/or estradiol level for the initiation of micronized progesterone to optimize natural proliferative phase (NPP) cryo-cycle outcome?
Authors: Stoop D , Dhaenens L , De Croo I , Vandierendonck F , Heindyckx B , Tilleman K , De Roo C , Vanden Meerschaut F , Rottiers A  S 
Published: July 2024

Study question

Is there an optimal follicular size and/or estradiol level for the initiation of micronized progesterone to optimize outcomes in NPP cycles potentially restricting scheduling flexibility?

Summary answer

All follicular sizes &gt;12 mm and estradiol levels &gt;120 pg./mL do not significantly correlate with ongoing pregnancy rates (OPR) or pregnancy loss (PL).

What is known already

Planning of a frozen embryo transfer (FET) is feasible within either a natural (NC) or artificial cycle (AC). While AC-FETs offer flexibility in planning, concerns have raised due to studies indicating a higher risk for obstetric complications. Conversely, NC-FETs show a protective effect against these complications but are usually less flexible in planning and ask for more monitoring. Recently, the natural proliferative phase (NPP) protocol was described, in which luteal phase support is initiated as soon as the endometrium reaches 7mm. NPP-FETs were associated with ongoing pregnancy rates comparable to AC- and NC-FETs.

Study design, size, duration

A retrospective single-centre study including a total of 300 consecutive single frozen embryo transfers (FET), performed at a tertiary fertility centre between March 2023 and December 2023. All cycles were single blastocyst transfer cycles retained from IVF/ICSI cycles with autologous oocytes.

Participants/materials, setting, methods

A total of 227 patients underwent one or more frozen embryo transfer cycles. Administration of MVP 800mg BID was initiated after fulfilling the following criteria: follicular size &gt; 12mm, estradiol level ≥120ng/mL and endometrium thickness ≥7mm. Blastocyst transfers were scheduled on the fifth day of MVP administration. Serum progesterone (P4) levels were determined on the day of transfer. Associations between treatment outcome, patient and cycle characteristics were explored using generalized estimating equations analyses.

Main results and the role of chance

The follicular size and estradiol level on the day of MVP initiation was not significantly associated with pregnancy rate (PR), ongoing pregnancy rate (OPR) or pregnancy loss (PL) (p = 0.386 and p = 0.260; p = 0.830 and p = 0.467; p = 0.978 and p = 0.313 respectively).

Mean number of visits needed prior to the initiation of the MVP for scheduling the embryo transfer was 2.4 (SD 1.3). PR, but not OPR, was significantly associated with both the duration of the follicular phase as well as the number of visits (p = 0.008 and p = 0.006 respectively). For 91.3 % (274/300) of patients, embryo transfer could be scheduled on a weekday.

49% (146/300) of patients had a positive hCG test after the fresh blastocyst transfer in the NPP cycle. Ongoing pregnancy rate was 35 % (104/300), whereas pregnancy loss (early clinical miscarriage and biochemical pregnancy) was 23% (33/146).

The OPR was significantly related to the age of the patient (p = 0.029). Both the PR as the OPR were significantly related the blastocyst quality (p = 0.008 and 0.009 respectively). The incidence of pregnancy loss was only significantly associated with blastocyst quality (p = 0.027). Mean serum P4 level at day of transfer was 19.4 ng/ml (SD 6.1) with a P4 level above 10ng/ml in 97% of cycles.

Limitations, reasons for caution

The retrospective character is a limitation of this study as well as the absence of live birth rate as a clinical outcome variable.

Wider implications of the findings

Flexibility about the required follicular sizes and estradiol levels open the perspective for exploring more flexible planning criteria such as lower thresholds for endometrial thickness. Further studies are needed to investigate whether ovulation occurs with formation of functional corpora lutea to effectively protect against hypertensive disorders.

Trial registration number

ONZ-2024-0015