# Impact of serum progesterone level on the day of embryo transfer on live birth rate after single frozen-thawed blastocyst transfer in hormone replacement therapy cycles

Audrey Pérennec, Thomas Goronflot, Florence Leperlier, Thomas Fréour, Maxime Chaillot

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## To cite this version:

Audrey Pérennec, Thomas Goronflot, Florence Leperlier, Thomas Fréour, Maxime Chaillot. Impact of serum progesterone level on the day of embryo transfer on live birth rate after single frozen-thawed blastocyst transfer in hormone replacement therapy cycles. Journal of Gynecology Obstetrics and Human Reproduction, 2025, 54 (9), pp.103024. 10.1016/j.jogoh.2025.103024. inserm-05357759

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Original Article

# Impact of serum progesterone level on the day of embryo transfer on live birth rate after single frozen-thawed blastocyst transfer in hormone replacement therapy cycles

Audrey Pérennec<sup>a</sup>, Thomas Goronflot<sup>c</sup>, Florence Leperlier<sup>a</sup>, Thomas Fréour<sup>a,b</sup>,
Maxime Chaillot<sup>a,*</sup>

<figure><img src="image_3.png" /></figure>

ARTICLE INFO

Keywords:

Live birth

Progesterone

Frozen-thawed embryo transfer

Prediction

ABSTRACT

**Purpose:** As the number of frozen-thawed embryo tryansfer cycles with Hormonal Replacement Therapy increases, the issue of the optimal progesterone level to ensure maximal success rates becomes critical. In this study, we aimed to determine the respective relevance of the 3 recently reported progesterone thresholds using an original statistical method.

**Methods:** This single-center retrospective study was conducted in a University-based Hospital in France in all consecutive single frozen thawed blastocyst transfers (SFBT) performed with HRT protocol in 2021. Progesterone levels were measured on the morning of the transfer. Patients were divided into deciles based on their progesterone levels on the day of SFBT, and outcomes were calculated for each decile. Multivariate logistic regression models were constructed to measure the association of these thresholds with clinical pregnancy rate and live birth rate (LBR), adjusting for demographic and clinical factors.

**Results:** A total of 256 cycles were included in the analysis. Clinical pregnancy rate was 30.1%, and live birth rate (LBR) was 29.3%. An inverted U curve was observed for the Positive Predictive Value of a LB, as it increases up to a peak around 11 ng/ml (optimal interval 10.5-12 ng/ml), before decreasing for high serum progesterone levels (>13 ng/ml).

**Conclusions:** Our study, aligned with recent literature, identified a positive relationship between progesterone levels on the day of SFBT in HRT and the positive predictive value of a live birth, the "ideal window" of progesterone on the day of FET being 10.5-12 ng/mL.

1. Introduction

In recent years, there has been a notable global increase in the utilization of Frozen Embryo Transfer (FET) cycles in Assisted Reproductive Technology (ART) [1]. Several factors may account for this surge, including advancements in embryo cryopreservation techniques, prolonged embryo culture with a single transfer policy, the widespread adoption of the "freeze-all" approach to mitigate ovarian hyperstimulation risk [2-4], and specific scenarios favoring FET [5,6]. Various endometrial preparation protocols exist today, encompassing spontaneous cycles, softly stimulated cycles, and cycles involving Hormone Replacement Therapy (HRT). Current evidence suggests comparable

pregnancy and live birth rates (LBR) among spontaneous cycles, softly stimulated cycles, and HRT cycles [2,7-10]. It is however worth noting that some studies report a slightly higher early miscarriage rate and more obstetrical complications with HRT cycles as compared to other protocols [7,11].

The HRT cycle involves a substitution protocol necessitating daily hormonal intake to artificially replicate the implantation window, mirroring the physiological menstrual cycle. This protocol initiates with natural estrogen intake at the cycle's onset to facilitate endometrial growth. Once the target endometrial thickness and triple-line appearance are achieved, progesterone is introduced five days before blastocyst transfer, preparing the endometrium for implantation and supporting

<footnote><sup>a</sup> Service de biologie et médecine de la reproduction, CHU de Nantes, CHU Nantes, Nantes Université, 38 Boulevard Jean Monnet, 44093 Nantes, France</footnote>

<footnote><sup>b</sup> Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, CHU Nantes, INSERM, F-44000 Nantes, France</footnote>

<footnote><sup>c</sup> Nantes Université, CHU Nantes, Pôle Hospitalo-Universitaire 11: Santé Publique, Clinique des données, INSERM, CIC 1413, F-44000 Nantes, France</footnote>

<footnote>* Corresponding author at: Service de médecine et biologie de la reproduction, CHU de Nantes, 38 boulevard Jean Monnet, 44093 Nantes cedex 01, France.
E-mail address: maxime.chaillot@chu-nantes.fr (M. Chaillot).</footnote>
<figure><img src="image_4.png" /><figcaption>Fig. 1. Flow chart. FET = frozen embryo transfer, SFBT = Single Frozen Blastocyst Transfer.</figcaption></figure>

the luteal phase [7,12]. The combined administration of natural estro-
gens and progesterone typically continues for approximately 10 weeks,
allowing sufficient endogenous hormone secretion for trophoblast
takeover. Of note, the vaginal route is mostly used for progesterne
administration in Europe. Despite widespread usage, there is currently
no consensus on the optimal dosage and preferred route of progesterone
administration, with these determined by progesterone availability, and
clinician and patient preferences. Recent studies underscore a critical
threshold level of circulating progesterone during HRT cycles, below
which pregnancy rates [13–15] and live birth rates decrease [13,16–19],
while miscarriage rates increase [17,19,20].

However, most published thresholds rely on population-specific cut-
offs, vary in methodology, and do not account for inter-individual
variability or clinical applicability. The prognostic utility of serum
progesterone on the day of transfer remains debated, and associations
with outcomes often appear modest. In this context, we aimed to test
whether previously proposed progesterone thresholds (8.8–10.0 ng/mL)
[15–17] are valid in our cohort. We also applied an alternative and
clinically oriented statistical approach, based on positive predictive
value (PPV), to determine whether an "optimal range" of progesterone
could be identified in HRT cycles involving single frozen-thawed blas-
tocyst transfer (SFBT).

## 2. Materials and methods

### 2.1. *Study population and method*

This single-center retrospective study was conducted at a university-
based hospital in France between April and October 2021. It included all
consecutive SFBT in HRT cycles in women aged 18 to 43 years at the

time of oocyte retrieval. Serum progesterone levels were measured on
the morning of embryo transfer in one of our two referenced labora-
tories, using a standardized electrochemiluminescence immunoassay
(Roche Diagnostics®).

Exclusion criteria were as follows: cycles involving oocyte or sperm
donation, cycles with pre-implantation genetic testing (PGT), sponta-
neous or softly stimulated cycles, delayed progesterone administration
(e.g., intramuscular route), and double embryo transfers. We also
excluded patients whose progesterone level was not measured using our
standardized assay. These exclusions aimed to ensure sample homoge-
neity and reduce confounding from heterogeneous stimulation or em-
bryo selection protocols.

### 2.2. *Protocol of frozen embryo transfer under hormone replacement therapy*

All patients followed a standardized protocol. On day 1 or 2 of the
menstrual cycle, endometrial preparation was initiated using oral
(Provames® 2 mg: 6–8 mg/day) or transdermal estradiol (Vivelledot®
or Oesclim® 75 µg: 150–225 µg/day). On day 15, a transvaginal ultra-
sound confirmed endometrial thickness ≥6 mm with a triple-line
pattern. If not achieved, estradiol dosage could be increased, or the
treatment prolonged. The cycle was cancelled if the endometrium
remained <6 mm. Micronized vaginal progesterone (Utrogestan® or
Progestan® 200 mg: 800 mg/day) was introduced 5 days prior to blas-
tocyst transfer. Estradiol dosage was increased on the evening of embryo
transfer, while progesterone dosage remained unchanged. Embryo
transfer was performed under transabdominal ultrasound guidance
using a Guardia™ AccessET catheter (Cook Medical). A serum preg-
nancy test was performed 11–12 days after embryo transfer. HRT was
<table><caption>**Table 1**
Clinical characteristics of the population.</caption><thead><tr><th></th><th>Study sample<br>(n = 256)</th><th>Missing data<br>(%)</th></tr></thead><tbody><tr><td>Oocyte age, years</td><td>32.40 ± 4.63</td><td>19.9</td></tr><tr><td>Maternal age, years</td><td>34.12 ± 4.50</td><td>0.0</td></tr><tr><td>BMI, kg/m²</td><td>24.91 ± 5.48</td><td>0.0</td></tr><tr><td>Smoking habits, n (%)</td><td>51 (19.9)</td><td>0.0</td></tr><tr><td>History, n (%)</td><td></td><td>0.0</td></tr><tr><td>No</td><td>156 (60.9)</td><td></td></tr><tr><td>Uterine surgery</td><td>68 (26.6)</td><td></td></tr><tr><td>Repeated miscarriages and implantation failure</td><td>26 (10.2)</td><td></td></tr><tr><td>Uterine surgery and repeated miscarriages or implantation failure</td><td>6 (2.3)</td><td></td></tr><tr><td>Type of infertility, n (%)</td><td></td><td>0.0</td></tr><tr><td>Primary</td><td>93 (36.3)</td><td></td></tr><tr><td>Primary-secondary</td><td>69 (27.0)</td><td></td></tr><tr><td>Secondary</td><td>94 (36.7)</td><td></td></tr><tr><td>Main infertility cause, n (%)</td><td></td><td>0.0</td></tr><tr><td>Dysovulation</td><td>49 (19.1)</td><td></td></tr><tr><td>Diminished ovarian reserve</td><td>22 (8.6)</td><td></td></tr><tr><td>Tubal infertility</td><td>9 (3.5)</td><td></td></tr><tr><td>Endometriosis</td><td>8 (3.1)</td><td></td></tr><tr><td>Male infertility</td><td>26 (10.2)</td><td></td></tr><tr><td>Mixed</td><td>47 (18.4)</td><td></td></tr><tr><td>Multiple female causes</td><td>28 (10.9)</td><td></td></tr><tr><td>Unexplained infertility</td><td>26 (10.2)</td><td></td></tr><tr><td>Genetic</td><td>41 (16.0)</td><td></td></tr><tr><td>Donation/Preimplantation genetic diagnosis, n (%)</td><td></td><td>0.0</td></tr><tr><td>No</td><td>156 (60.9)</td><td></td></tr><tr><td>Oocyte donation</td><td>50 (19.5)</td><td></td></tr><tr><td>Sperme donation</td><td>8 (3.1)</td><td></td></tr><tr><td>Preimplantation genetic diagnosis</td><td>42 (16.4)</td><td></td></tr><tr><td>AMH, ng/ml</td><td>2.98 [1.75, 5.11]</td><td>19.1</td></tr><tr><td>AFC</td><td>23.00 [16.00, 35.00]</td><td>26.6</td></tr><tr><td>ICSI, n(%)</td><td>153 (59.8)</td><td>0.0</td></tr><tr><td>Route of administration for estradiol, n (%)</td><td></td><td>0.0</td></tr><tr><td>Oral</td><td>188 (73.4)</td><td></td></tr><tr><td>Transdermal</td><td>67 (26.2)</td><td></td></tr><tr><td>Duration of treatment until transfer, day</td><td>27.00 [25.00, 30.00]</td><td>0.0</td></tr><tr><td>Endometrial thickness, mm</td><td>8.13 ± 1.82</td><td>0.0</td></tr><tr><td>Type of embryo transferred, n (%)</td><td></td><td>0.0</td></tr><tr><td>Day-5</td><td>226 (88.3)</td><td></td></tr><tr><td>Day-6</td><td>30 (11.7)</td><td></td></tr><tr><td>Blastocyst quality, n (%)</td><td></td><td>0.0</td></tr><tr><td>Excellent</td><td>114 (44.5)</td><td></td></tr><tr><td>Good</td><td>84 (32.8)</td><td></td></tr><tr><td>Average</td><td>58 (22.7)</td><td></td></tr><tr><td>Implantation rate, n (%)</td><td>130 (50.8)</td><td>0.0</td></tr><tr><td>Pregnancy outcomes, n (%)</td><td></td><td>0.0</td></tr><tr><td>No pregnancy</td><td>126 (49.2)</td><td></td></tr><tr><td>Ongoing pregnancy</td><td>77 (30.1)</td><td></td></tr><tr><td>Miscarriage</td><td>51 (19.9)</td><td></td></tr><tr><td>Ectopic pregnancy</td><td>2 (0.8)</td><td></td></tr><tr><td>Live birth rate, n (%)</td><td>75 (29.3)</td><td>0.0</td></tr></tbody></table>

Legend: Data are presented as means +/- SD or medians [inter-quartile range] or numbers (percentages). BMI = body mass index; AMH = anti-mullerian hormone; AFC = antral follicle count; ICSI = intracytoplasmic sperm injection.

continued until 10 weeks of gestation. Ongoing pregnancy was defined as the presence of a gestational sac with fetal cardiac activity at or beyond 12 weeks.

## 2.3. Embryo parameters

Embryos originated from IVF or ICSI cycles and were cultured to the blastocyst stage using a time-lapse system (Embryoscope®, Vitrolife) with single-step medium (G-TL®, Vitrolife) under low oxygen conditions. Blastocysts ≥B2 on day 5 and ≥B4 on day 6 were cryopreserved, except those with grade C trophectoderm. Morphological quality was classified as excellent (≥3AA), good (3–6AB, 3–6BA, B2), or average

(3–6BB, 3–6CA, 3–6CB, B1). Vitrification and warming were performed using Vit Blast® and Warm Blast® kits (Vitrolife), respectively.

## 2.4. Progesterone measurement

Serum progesterone was measured the morning of embryo transfer, within six hours after the last vaginal progesterone dose. All assays were performed using the same electrochemiluminescence immunoassay platform (Roche Diagnostics®). The physician performing the transfer was blinded to the progesterone results.

## 2.5. Statistical analysis

Quantitative variables were expressed as means ± standard deviation or medians with interquartile ranges. Qualitative variables were reported as counts and percentages. No missing data were observed for the primary or secondary outcomes or for progesterone measurements.

To test previously established progesterone thresholds (8.8 ng/mL, 9.8 ng/mL, and 10.0 ng/mL) [15–17], we performed univariate and multivariate logistic regression analyses adjusted for confounding factors (maternal age, BMI, embryo quality). Patients were also grouped by progesterone deciles to explore trends.

To better assess the clinical utility of progesterone levels, we calculated the positive predictive value (PPV) for live birth and clinical pregnancy outcomes at each integer level of progesterone (1–15 ng/mL), with 95 % confidence intervals estimated using bootstrap resampling (3000 iterations). We also conducted subgroup analyses stratified by maternal age (<35 vs ≥35 years), BMI (<25 vs ≥25 kg/m²), and embryo quality (excellent, good and average).

A receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis were added to evaluate the discriminatory power of serum progesterone for predicting live birth.

## 2.6. Ethics approval

This study received ethical approval from the Groupe Nantais d'Éthique dans le Domaine de la Santé (GNEDS) under reference 23–76–06–082

# 3. Results

Of the 333 patients initially screened, 256 were included in the final analysis after excluding double blastocyst transfers (n = 13), non-HRT protocols (n = 3), and cycles in which serum progesterone was not measured using the standardized assay (n = 61) (Fig. 1). Demographic and clinical characteristics are summarized in Table 1. The clinical pregnancy rate was 30.1 %, and the live birth rate (LBR) was 29.3 %.

On the day of embryo transfer, the mean serum progesterone level was 10.71 ng/mL (SD = 4.37). Respectively, 63.7 %, 54.3 %, and 50.8 % of patients had progesterone values above the published thresholds of 8.8, 9.8, and 10.0 ng/mL.

Patients were divided into deciles based on their progesterone levels to explore potential trends in reproductive outcomes. We observed that implantation rate, clinical pregnancy rate, and LBR gradually increased with progesterone levels, peaking around 12 ng/mL (Fig. 2). However, this increase was not statistically significant in multivariate analysis, and no clear association was detected below 12 ng/mL. Moreover, previously published thresholds [15–17] ranging from 8.8 to 10.0 ng/mL were not associated with higher LBR in our population (Fig. 3). These findings suggest that these thresholds may lack external validity and are not universally applicable.

We then used a predictive model based on PPV to assess the likelihood of live birth at various progesterone levels. An inverted U-shaped curve was observed: PPV increased with progesterone concentration, peaking between 10.5 and 12 ng/mL (yielding PPVs of 35–36.6 %), before declining beyond 13 ng/mL (Fig. 4). For instance, the PPV for live
<figure><img src="image_5.png" /><figcaption>Fig. 2. Live birth rates according to serum progesterone deciles on the day of transfer. Rates are expressed as percentages with a 95 % confidence interval, serum progesterone levels are expressed in ng/ml. The dotted line represents the live birth rate in our study sample (n = 256). The vertical lines corresponding to the thresholds to be replicated were drawn in order to assess their clinical relevance in a univariate manner.</figcaption></figure>

<figure><img src="image_6.png" /><figcaption>Fig. 3. Odds ratio for pregnancy outcomes in patients with a progesterone level on the day of transfer above the thresholds tested, compared with patients with a progesterone level below the thresholds. OR: Odds-Ratios; 95 % CI: 95 % confidence interval.</figcaption></figure>
<figure><img src="image_7.png" /><figcaption>Fig. 4. Positive predictive value (IC95 %) for live birth according to the progesterone level on the day of transfer.</figcaption></figure>

birth was 30.2 % at 6 ng/mL, 33.3 % at 9 ng/mL, and 36.6 % at 11 ng/mL. A similar pattern was observed for clinical pregnancy (data not shown).

Subgroup analyses were performed to explore whether progesterone levels had differential effects according to maternal age, BMI, and embryo quality. Trends similar to the main analysis were observed (Figs. 5–11). Notably, the number of patients with serum progesterone levels >12 ng/mL was relatively low, limiting our ability to draw firm conclusions regarding high-range progesterone.

The AUC was 0.56, indicating a limited predictive value (Fig. 12). These results reinforce the modest strength of association between serum progesterone and clinical outcome.

# 4. Discussion

## 4.1. Main findings and interpretation

In this retrospective study, we observed a modest and statistically weak association between serum progesterone levels on the day of

embryo transfer and LBR in HRT cycles using SFBT. While traditional threshold analyses failed to replicate previously published cut-offs (8.8–10.0 ng/mL), our alternative approach using PPV analysis suggested an “optimal window” between 10.5 and 12 ng/mL. Within this range, PPV for live birth increased slightly to 35–36.6 %. However, this gain remains limited, as demonstrated by an AUC of 0.56, underscoring the low discriminative power of serum progesterone in isolation. PPV, however, may offer greater clinical applicability than odds ratios by more directly reflecting the probability of success for individual patients.

## 4.2. Comparison with existing literature

Multiple studies since 2015 have reported lower thresholds for progesterone below which outcomes decline [13–17,19–23]. However, these studies vary significantly in design, population characteristics, progesterone formulations, and timing of measurement. While our cohort had broadly similar demographic profiles, we did not observe significant associations at the previously published thresholds. Instead,
<figure><img src="image_8.png" /><figcaption>Fig. 5. Positive predictive value (IC95 %) for live birth according to the progesterone level on FET day among women aged <35 years.</figcaption></figure>

our data suggest a weak, continuous relationship between progesterone levels and outcome, with a decline in success beyond 13–14 ng/mL.

This observation aligns with prior data indicating potential deleterious effects of supraphysiological progesterone levels [13,22,24], possibly due to premature endometrial maturation and embry-o-endometrium asynchrony. In 2015, Yovich et al. [13] reported reduced clinical pregnancy rates for progesterone ≥100 nmol/L (31.4 ng/mL). Similarly, Alyasin et al. [22] described a significant drop in LBR beyond 32.5 ng/mL. These findings reinforce the need to consider not only a lower threshold, but also an upper limit for optimal serum progesterone levels. However, given the relatively small number of patients with high progesterone levels in our cohort, further confirmation is needed in larger populations.

### 4.3. Subgroup analyses

Subgroup analyses by maternal age, BMI, and embryo quality did not reveal significant differences, though a trend similar to the main analysis persisted. These results suggest that the effect of serum progesterone may be largely independent of these variables, but the low number of patients with high progesterone (>12 ng/mL) prevents strong conclusions in this range.

### 4.4. Biological and clinical considerations

Despite widespread use, serum progesterone monitoring in HRT cycles remains controversial. The vaginal route is most commonly used in Europe due to its capacity to achieve high intra-uterine concentrations [25]. However, serum levels show considerable inter-individual
<figure><img src="image_9.png" /><figcaption>Fig. 6. Positive predictive value (IC95 %) for live birth according to the progesterone level on FET day among women aged ≥35 years.</figcaption></figure>

variability, influenced by factors such as age, BMI, absorption kinetics, and the timing of the last dose [15,23,26].

Studies have reported a positive association between maternal age and serum progesterone, and a negative association with BMI or delayed sampling [15,23]. This pharmacokinetic variability complicates the interpretation of serum levels and limits the reliability of fixed thresholds.

Alternative strategies, including the addition of subcutaneous (e.g., Progiron®) or oral progesterone (e.g., dydrogesterone, Duphaston®), have been proposed [27], although the safety of some molecules in HRT cycles is still debated [28]. Importantly, increasing the vaginal dose beyond 800–1000 mg/day appears to exceed the saturation threshold for absorption [16,28], with no clear benefit and potential risks. Excess progesterone could lead to asynchronous endometrial advancement and impaired implantation [24].

Thus, before implementing routine dose adjustments based solely on serum levels, further research is needed to clarify the interplay between administration route, pharmacokinetics, and endometrial response.

### 4.5. Strengths of the study

This study presents several methodological and conceptual strengths. First, it introduces an original approach based on the PPV, which may offer more clinically relevant insight than traditional statistical associations such as odds ratios, particularly when guiding individual patient counseling. The use of a standardized and validated progesterone assay across all participants ensures consistency and enhances the reliability of measurements. Data were collected prospectively with minimal missing information, reinforcing the robustness of the dataset. The design of the study was single-blinded, as clinicians
<figure><img src="image_10.png" /><figcaption>Fig. 7. Positive predictive value (IC95 %) for live birth according to the progesterone level on FET day among women with BMI ≤ 25 kg/m².</figcaption></figure>
<figure><img src="image_11.png" /><figcaption>Fig. 8. Positive predictive value (IC95 %) for live birth according to the progesterone level on FET day among women with BMI > 25 kg/m².</figcaption></figure>

performing the embryo transfer were unaware of serum progesterone levels at the time of transfer, thereby minimizing performance bias. In addition, the analysis adjusted for key potential confounding factors, including a clear distinction between oocyte age (age at retrieval) and maternal age (age at transfer), a detail often omitted in other studies despite its known relevance in ART outcomes. Finally, our choice to use live birth as the primary endpoint, rather than surrogate outcomes such as implantation or clinical pregnancy, adds further clinical value to the results. The application of bootstrap resampling techniques further strengthens the internal validity of our statistical analyses by accounting for the limited sample size.

## 4.6. Limitations and need for replication

Limitations must be acknowledged. The single-center design and moderate sample size (n = 256) limit the external validity of our findings, particularly for progesterone levels >12 ng/mL. The absence of a

validation cohort or prospective confirmation limits our ability to make definitive clinical recommendations. Moreover, while our cohort reflects real-world diversity—including patients with previous implantation failure, uterine anomalies, and donor gametes (excluding PGT-A)—this heterogeneity may introduce confounding.

## 5. Conclusion

In conclusion, our study, aligned with recent literature, identified a positive relationship between progesterone levels on the day of SFBT in HRT and the positive predictive value of a live birth, the "ideal window" of progesterone on the day of FET being 10.5–12 ng/mL. Although we used an original and clinically relevant statistical method, the predictive value of progesterone level remains relatively weak, especially as long as it has not been validated on a replication cohort. Therefore, the use of a strict threshold for progesterone level in HRT cycles should still be considered with care and hasty changes in practices should be avoided,
<figure><img src="image_12.png" /><figcaption>**Fig. 9.** Positive predictive value (IC95 %) for live birth according to the progesterone level on FET day in transfers involving embryos of excellent morphological quality (≥3AA).</figcaption></figure>
<figure><img src="image_13.png" /><figcaption>**Fig. 10.** Positive predictive value (IC95 %) for live birth according to the progesterone level on FET day in transfers involving embryos of good morphological quality (3–6AB, 3–6BA, B2).</figcaption></figure>
<figure><img src="image_14.png" /><figcaption>**Fig. 11.** Positive predictive value (IC95 %) for live birth according to the progesterone level on FET day in transfers involving embryos of average morphological quality (3–6BB, 3–6CA, 3–6CB, B1).</figcaption></figure>

<figure><img src="image_15.png" /><figcaption>**Fig. 12.** Receiver Operating Characteristic (ROC) curve for live birth prediction based on serum progesterone levels on the day of embryo transfer.</figcaption></figure>

especially if they lead to excessive and potentially deleterious progesterone supplementation. Prospective randomized studies are essential to confirm the notion of an optimal progesterone interval on the day of FET in HRT cycles. Additional research is also warranted to explore therapeutic adaptations, such as modifications in dosage and/or route of administration.

Declaration of competing interest

The authors have no relevant financial or non-financial interests to disclose

Acknowledgements

None

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