COMPARISON OF ONGOING PREGNANCY RATES BETWEEN NATURAL PROLIFERATIVE PHASE AND MODIFIED NATURAL CYCLE PROTOCOLS IN FROZEN BLASTOCYST TRANSFERS

Abstract

Objective

The Natural Proliferative Phase (NPP) frozen embryo transfer (FET) protocol is an emerging method with increasing reports in the literature. Unlike conventional natural cycle FET protocols, the NPP protocol offers flexibility in FET timing and potentially avoids increased rates of perinatal complications due to the absence of corpus luteum in artificial cycles. This study aims to share the initial results of our clinic's first trials with the NPP protocol and to investigate its impact on ongoing pregnancy rates (OPRs) compared to the modified natural cycle (mNC) protocol.

Materials and Methods

This retrospective cohort study included cycles with single blastocyst embryo transfers without preimplantation genetic testing at Hacettepe University IVF Unit, between June 2022 and June 2024. Each patient was included with a single cycle. The choice of endometrial preparation protocol was based on scheduling embryo transfers on weekdays. In the mNC protocol, when the leading follicle diameter was 14-21 mm, endometrial thickness was ≥7 mm, and serum progesterone was <1.5 ng/ml, rhCG 250 mg was administered, vaginal progesterone (P) 3 × 200 mg was initiated 4 days after hCG trigger, and blastocyst transfer was performed 7 days after hCG trigger. In the NPP protocol, with the same criteria, vaginal P 3 × 200 mg and subcutaneous P 1 × 1 were started. Blastocyst transfer was performed 5 days after starting P. The primary outcome was ongoing pregnancy, defined as the presence of an intrauterine fetal heartbeat. Secondary outcomes included positive pregnancy test (serum beta-HCG >5 IU/L 9 days post-transfer) and clinical pregnancy (visualization of an intrauterine gestational sac).

Results

The study included 52 cycles, with 17 NPP and 35 mNC single blastocyst transfer cycles. The mean age, BMI, and infertility duration were 32.85 ± 4.01 years, 23.73 [IQR: 21.63, 26.20] kg/m², and 41.00 [IQR: 29.00, 60.75] months, respectively, with no significant differences between the NPP and mNC groups. There were no significant differences in positive pregnancy test rates (9/17 [53%] vs. 21/35 [60%], p=0.629), clinical pregnancy rates (6/17 [35%] vs. 20/35 [57%], p=0.139), and OPRs (5/17 [29%] vs. 18/35 [51%], p=0.134). According to univariate logistic regression, the odds ratio (OR) of having an ongoing pregnancy in NPP cycles was 0.39 [95% CI: 0.11-1.30] compared to the mNC protocol. Multivariate logistic regression, adjusted for age, BMI, infertility duration, cycle number, number of blastocysts transferred, and embryo quality, showed an OR of 0.43 [95% CI: 0.09-1.74] for ongoing pregnancy in NPP cycles compared to the mNC protocol.

Conclusions

The initial results from our clinic indicate that pregnancy outcomes between NPP and mNC protocols are not significantly different. Further randomized controlled trials or cohort studies with larger sample sizes are necessary to avoid type II error and establish the non-inferiority of the newly implemented NPP protocol.