Background and Methodology

The gonadotropin-releasing hormone antagonist (GnRH-ant) protocol is a common approach for ovulation induction in IVF-ET, favored for its shorter duration, reduced gonadotropin (gn) usage, and lower risk of ovarian hyperstimulation syndrome (OHSS). However, GnRH-ant cycles can also lead to elevated progesterone levels on the trigger day (P_trigger). A P_trigger level of 1.5 ng/mL or higher is often considered elevated and can negatively impact endometrial receptivity, potentially hindering embryo implantation.

The retrospective analysis examined clinical data from women undergoing IVF-ET assisted reproduction at a hospital’s Reproductive Medicine Department between january 2019 and December 2023. Strict exclusion criteria were applied,including ovarian diseases,uterine abnormalities,endocrine-related diseases,and chromosomal abnormalities,ensuring a focused analysis on a specific patient demographic.

On day 2 or 3 of the menstrual cycle, researchers measured antral follicle count (AFC) and sex hormone levels. Participants then underwent ovulation induction with recombinant follicle-stimulating hormone, with dosages adjusted based on follicular growth and hormone levels. Cetrorelix acetate, a GnRH antagonist, was introduced starting on day 5 or 6 of ovulation induction to prevent premature ovulation. Ovulation was triggered with recombinant human chorionic gonadotropin (hCG) when at least one follicle reached a diameter of ≥ 18 mm or at least three follicles measured ≥ 16 mm in diameter, signaling optimal follicular maturity.

The decision to proceed with fresh embryo transfer, freezing, or extended culture to the blastocyst stage was made three days after oocyte retrieval, considering endometrial condition, embryo quality, and other clinical factors. Luteal phase support was provided to participants who underwent fresh embryo transfer to enhance endometrial receptivity and support early pregnancy.

A β-human chorionic gonadotropin (hCG) level > 10 U/L, measured 14 days post-embryo transfer, was defined as hCG-positive, indicating a biochemical pregnancy. A clinical pregnancy was confirmed by transvaginal ultrasound between 28 and 35 days post-embryo transfer, indicated by the presence of a gestational sac within the uterine cavity, marking a viable pregnancy.

Key Findings

The study categorized cycles into four groups based on the P_trigger/bP ratio: group A (P_trigger/bP trigger/bP ≥ 2 and trigger/bP ≥ 3. The researchers then compared general data, ovulation induction status, and fresh embryo transfer outcomes between these groups to identify potential correlations.

The study revealed that women in the pregnant group were considerably younger, had a shorter duration of infertility, received a lower total Gn dose, had a higher AFC, and more oocytes were retrieved compared to the non-pregnant group. However, basal estradiol (bE₂) levels, bP levels, P_trigger levels, and the P_trigger/bP ratio did not differ significantly between the two groups, suggesting that these factors alone may not determine pregnancy success.

Multivariate logistic regression analysis identified age as a notable factor associated with clinical pregnancy outcomes, reinforcing existing research on the impact of age on IVF success rates. This highlights the importance of considering age as a primary factor in fertility treatment planning.

When comparing the groups with varying P_trigger/bP ratios, the study observed that bP levels decreased across the groups (group A > group B > group C > group D), while P_trigger levels increased (group A P_trigger/bP ratio of ≥ 2, especially those reaching a ratio of 3, showed a consistent trend of significantly higher levels of total Gn doses, E₂ levels on trigger day, and more retrieved oocytes than other groups.

Moreover, an increase in the P_trigger/bP ratio was associated with a gradual decline in both the implantation rates and the clinical pregnancy rates. Group D, where the P_trigger/bP ratio was ≥ 3, had significantly lower embryo implantation and clinical pregnancy rates than Group A, where the P_trigger/bP ratio was trigger/bP ratios and better outcomes in fresh embryo transfer (IVF-ET).

To control for age-related confounding factors, a 1:1 propensity score matching was performed between groups A and D. The results showed that, prior to matching, women in group A were younger, received a lower total Gn dose, had lower trigger day E₂ levels, lower P_trigger levels, and fewer oocytes retrieved, compared to group D. After matching, women in group A (P_trigger/bP 2 levels, lower P_trigger, and higher bP levels compared to those in group D (P_trigger/bP ≥ 3).

ROC curve analysis revealed that the AUC for the predictive power of P_trigger/bP ratio for clinical pregnancy after fresh embryo transfer was 0.538, indicating limited diagnostic utility. The sensitivity and specificity were 0.850 and 0.2

Unveiling the Mystery: Is the P_trigger/bP Ratio the Key to IVF-ET Success?

Does a simple ratio hold the key to unlocking higher success rates in in-vitro fertilization and embryo transfer (IVF-ET)? The answer, it turns out, is more nuanced than initially believed.

Interviewer: Dr.Anya Sharma, a leading expert in reproductive endocrinology and infertility, welcome to World Today News. Yoru recent research on the P_trigger/bP ratio and its impact on IVF-ET outcomes has generated notable interest.Can you explain, for our readers, what exactly the P_trigger/bP ratio represents and why it’s significant in the context of IVF?

Dr. Sharma: Thank you for having me. The P_trigger/bP ratio is a relatively new metric in assisted reproductive technology (ART) that assesses the change in progesterone levels. Specifically,it compares the progesterone level at the time of ovulation triggering (P_trigger) to the basal progesterone level (bP) measured earlier in the menstrual cycle.Its importance stems from the fact that progesterone plays a crucial role in both ovarian function and endometrial receptivity—key factors determining the success of embryo implantation and subsequent pregnancy.A balanced progesterone profile is essential for a fertile environment, and this ratio helps us understand that dynamic.

Interviewer: Your study focused on women under 35 with normal ovarian reserve undergoing their frist IVF-ET cycle. Why this specific demographic?

Dr.Sharma: We chose this demographic to isolate the effect of the P_trigger/bP ratio without the confounding factors often observed in older women or those with compromised ovarian reserve. These women represent a relatively homogenous population, simplifying the analysis and allowing us to focus on the relationship between the ratio and IVF outcomes. This approach enables a clearer understanding of the ratio’s potential predictive value in this specific, but significant, patient group.

Interviewer: Your findings suggest a correlation between the P_trigger/bP ratio and IVF-ET success rates. Can you elaborate on what you discovered?

Dr. Sharma: Our research indicates a potential, though not definitive, correlation. We observed that women with a lower P_trigger/bP ratio, especially those below a threshold of 2, exhibited higher rates of clinical pregnancies and implantation rates compared to those with higher ratios. this suggests that elevated progesterone levels before triggering ovulation may negatively impact endometrial receptivity. However, it is crucial to note that the P_trigger/bP ratio is not on its own a strong predictive marker, as reflected in the AUC of 0.538 from our ROC curve analysis; the area under the curve for the pregnancy predictive value was limited. This indicates the model doesn’t always accurately predict who will and won’t get pregnant, highlighting that other factors are equally or more important.

Interviewer: What are some of the potential implications of this research for clinical practice? How can reproductive endocrinologists utilize this information?

Dr. Sharma: While the P_trigger/bP ratio isn’t a definitive predictor, it can serve as a valuable additional piece of information when evaluating a patient. Clinicians can use it in conjunction with other metrics like antral follicle count (AFC),basal estradiol levels (bE₂),and assessment of ovarian response (using Gn,or gonadotropin,dosage and total egg retrieval). By monitoring the P_trigger/bP ratio, clinicians may be able to identify patients at higher risk of reduced endometrial receptivity, possibly allowing for more tailored treatment strategies. This includes things like adjusting the ovulation triggering protocol or optimizing luteal phase support, though more research is needed to determine effective practices based on specific P_trigger/bP outcomes.

Interviewer: What are the next steps in this area of research? What questions remain unanswered?

Dr. Sharma: Further research is crucial before firm recommendations can be made about standard clinical practice. We need larger, prospective studies with diverse patient populations to validate our findings and determine the clinical utility of the P_trigger/bP ratio more comprehensively. It is indeed also vital that further investigation of potential causative factors for elevated progesterone levels at the time of ovulation triggering in IVF-ET is needed also. Understanding those mechanisms will be critical to developing targeted interventions.

Interviewer: Thank you,Dr. Sharma, for sharing your insights. This has been incredibly informative. For our readers,this research sheds light on the complexities of IVF-ET and underscores the continuing need for further research in reproductive endocrinology to advance the success rates of assisted reproductive technologies (ART).

Dr. Sharma: Thank you. The journey to parenthood is a challenging one for many couples, and research in this area is crucial for improving outcomes.

Key Takeaways:

The P_trigger/bP ratio is a newly emerging metric in assessing the change in progesterone levels during IVF-ET cycles.

A lower P_trigger/bP ratio may be associated with improved IVF-ET outcomes,though further research is needed.

This ratio should be used in conjunction with other clinical markers to make informed clinical decisions.

Larger, prospective studies are required to solidify understanding the prognostic value of the ratio and its implications in clinical practice.

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