The efficiency of progesterone/estradiol and progesterone/follicle ratio without elevated trigger-day progesterone levels on the reproductive outcomes of GnRH antagonist IVF/ICSI cycles.

AIM: To assess the predictive value of serum progesterone/estradiol (P/E2) and serum progesterone/follicle (P/F) ratios on the reproductive outcomes of women without elevated trigger-day progesterone levels undergoing GnRH-antagonist IVF (in vitro fertilization)/ICSI (intracytoplasmic sperm injection) cycles. MATERIALS AND METHODS: This was a retrospective cohort study in a university teaching hospital conducted between January 2017 and December 2019. Couples who underwent assisted reproduction cycles were evaluated. Initially, 978 cycles were evaluated and only GnRH antagonist cycles (n = 505) without elevated trigger-day progesterone levels were analyzed after respecting exclusion criteria. RESULTS: A total of 505 cycles were analyzed after the exclusion criteria were met. The clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were 45.5%, 30.9%, and 27.8%, respectively. Cutoff values of P/E2 and P/F ratios that were discriminative for achieving or not achieving clinical pregnancy were 0.36 and 0.17, respectively. The clinical pregnancy rates were found to be significantly different between below and above P/E2 cutoff values (49.8% vs. 40.1%, respectively, p = .031), while there were no significant differences between below and above P/F cutoff values regarding the pregnancy outcomes. CONCLUSION: The P/E2 and P/F ratios were found to be more efficient and reliable markers than serum progesterone level alone in predicting the reproductive outcomes of assisted reproduction cycles without a premature rise in serum progesterone levels. A P/E2 ratio ≤0.36 and a P/F ratio ≤0.17 significantly improved the cycle outcomes.

Effect of progesterone/estradiol ratio on pregnancy outcome of patients with high trigger-day progesterone levels undergoing gonadotropin-releasing hormone antagonist intracytoplasmic sperm injection cycles: a retrospective cohort study.

This study investigates the predictive power of serum progesterone/estradiol (P/E2) level for estimating the live birth rate in patients who had a serum progesterone (P) rate ≥ 1.5 ng/mL on the human chorionic gonadotropin (hCG) administration day and who received the gonadotropin-releasing hormone (GnRH) antagonist protocol and intracytoplasmic sperm injection (ICSI). This retrospective cohort study included 176 cycles. The P/E2 ratio was lower in patients with a live birth (0.73 ± 0.54) than those without a live birth (1.05 ± 1.38), but the difference was not statistically significant (p = .158). According to the receiver operating characteristic curve analysis of the hCG day P/E2 ratio, the area under the curve was 0.579 (95% confidence interval: 0.478 - 0.680, p = .158) for predicting live birth. In conclusion, this study suggests that a P/E2 ratio is not a significant predictor of a live birth rate in the patients with an hCG-day serum progesterone level of ≥1.5 ng/mL undergoing GnRH antagonist ICSI cycles with a fresh embryo transfer. Impact statement What is already known on this subject? As the progesterone (P) levels in the late follicular phase correlate with the estradiol (E2) levels and the increase in mature follicles, earlier studies have proposed the trigger-day progesterone/estradiol (P/E2) ratio as a potential new marker for a premature luteinisation and live birth success. Most of these studies were conducted on long agonist cycles, and found that arbitrarily defined P/E2 ratio of >1 to be associated with poor pregnancy outcomes. What do the results of this study add? This study retrospectively examines the gonadotropin-releasing hormone (GnRH) antagonist cycles with a trigger-day serum P value of ≥1.5 ng/mL undergoing the intracytoplasmic sperm injection (ICSI) treatment. The receiver operating characteristic (ROC) curve analysis did not identify a statistically significant threshold value for the trigger-day P/E2 ratio that was beneficial in predicting a live birth. The P/E2 ratio was also lower in the cycles with a live birth than those without a live birth, although the difference was not statistically significant. What are the implications of these findings for clinical practice and/or further research? The trigger-day P/E2 ratio does not seem to be an efficient prognostic factor for a live birth in the GnRH antagonist ICSI cycles with a trigger-day serum progesterone level of ≥1.5 ng/mL. Further studies are needed to clarify the association of the trigger-day P/E2 ratio and the pregnancy outcomes in GnRH antagonist ICSI cycles.

Progesterone, progesterone/estradiol and ART outcomes in day-5 transfer cycles.

The objective of this study was to assess the effects of elevated luteal-phase progesterone levels (PE) and high progesterone/estradiol ratio ('P/E2' ratio) on IVF outcomes, exclusively in GnRH-antagonist cycles with day-5 embryo transfer. PE was not found to have a significant effect on implantation or clinical pregnancy rate (CPR) (OR 0.56, 95% CI 0.25-1.25, p = .16). Elevated 'P/E2' ratio (≥0.55) on trigger day was associated with a poorer response to stimulation and lower clinical pregnancy rates (OR 0.58, 95% CI 0.34-1.00, p = .05). Patients with PE and low 'P/E2' ratio yielded significantly more oocytes than patients with PE and high 'P/E2' ratio. The mean implantation rate per patient decreased by 60% in the group with PE and high 'P/E2' ratio in comparison to the group with PE and low 'P/E2' ratio (17.9%±36.6 vs. 45.5%±47.2, p = .06), although no statistical significance was observed. The detrimental effect of PE may be mitigated by culturing embryos to day-5 before embryo transfer. Combined assessment of serum progesterone and 'P/E2' ratio may predict pregnancy outcome better than progesterone levels alone.

Progesterone/Oestradiol ratio can Better Predict Intracytoplasmic Sperm Injection Outcomes than Absolute Progesterone Level.

BACKGROUND: Several parameters were proposed to predict the impact of premature luteinization on intracytoplasmic sperm injection (ICSI) outcomes such as isolated progesterone (P) level, progesterone to oocyte ratio, and progesterone/estradiol ratio (P/E2). AIM: The aim of this study is to compare the predictive value of P/E2 ratio and isolated P level on the ovulation triggering day for pregnancy outcomes in fresh GnRH antagonist ICSI cycles. SETTINGS AND DESIGN: A retrospective cohort study conducted in a university-affiliated in vitro fertilization center between January 2017 and April 2019. METHODS: The study included women who underwent their first- or second-ranked GnRH antagonist ICSI cycles with day-3 embryo transfer. P/E2 ratio was calculated as (P [ng/mL] × 1000)/E2 (pg/mL). Cutoff values of ≥1.5 ng/ml for high P (HP) and ≥0.55 for HP/E2 ratio were chosen based on the literature. STATISTICAL ANALYSIS: A receiver operating curve was performed to detect the predictability of serum P/E2 and P for the ongoing pregnancy rate. First, patients were divided according to either P level (low P < 1.5 ng/mL and HP ≥1.5 ng/mL) or P/E2 ratio (low P/E2 <0.55 and HP/E2 ≥ 0.55). Patients were further divided into four subgroups: (Group A: HP and HP/E2 ratio, Group B: low P and low P/E2 ratio, Group C: HP only, and Group D: HP/E2 only). A multivariate regression analysis models were used to account for the effect of the cycle confounders on the likelihood of pregnancy. RESULTS: A total of 402 ICSI cycles were analyzed. The area under the curve was 0.67 and 0.59 for P/E2 and P, respectively. P/E2 showed a significant association with ongoing pregnancy (adjusted odds ratios [aOR]: 0.409, 95% confidence interval [CI] 0.222-0.753, P = 0.004) while HP revealed no significant predictive value (aOR: 0.542, 95% CI 0.284-1.036, P = 0.064) after the multivariate analysis. CONCLUSIONS: P elevation may not present as an independent predictor for cycle outcomes. P/E2 ratio has a better prognostic value than P alone in predicting pregnancy of GnRH antagonist cycles.

Testosterone, the progesterone/estradiol ratio, and female ratings of masculine facial fluctuating asymmetry for a long-term relationship.

Idiosyncratic variation within the normal range of androgens levels in women account for significant variations in personality and behavior. We studied if testosterone introduces significant biases in women's perception of fluctuating symmetry of male faces suitability for a long-term relationship. Participants were 145 female college students asked to rate in a two-choice forced paradigm the attractiveness, suitability as a long-term partner, and economic success, fatherliness and fidelity of an asymmetric and a symmetric male face. Since our sample consists of random women interested in participating, whether for personal reasons or because they were paid to participate, we controlled for menstrual phase. All participants provided salivary samples to determine testosterone (T), estradiol (E2) and progesterone (P4) levels. When the P4/E2 was low and T low-to-normal, the symmetric face was rated as more attractive, and a desirable long-term partner, but these preferences changed to the opposite when P4/E2 was high. In high T women, neither face was rated as more attractive, independently from the P4/E2 ratio, but the asymmetric face was preferred as a long-term partner when conception risk was high, changing to prefer the symmetric face as the P4/E2 increased. The overall perception of male faces was that the symmetric face was more economical successful but a poor parent and highly unfaithful compared to the asymmetric face. A significant interaction between T and P4/E2 for ratings success of the asymmetric face suggests that high levels of feminine T might be related to inter-sexual competition when conception risk is high.

Do increased levels of progesterone and progesterone/estradiol ratio on the day of human chorionic gonadotropin affects pregnancy outcome in long agonist protocol in fresh in vitro fertilization/intracytoplasmic sperm injection cycles?

BACKGROUND: The effect of elevated levels of serum progesterone (P4) and estradiol (E2) on the day of human chorionic gonadotropin and their cut-off value on in vitro fertilization (IVF) outcomes is still not clear. AIMS: The aim was to evaluate the association between serum P4, E2 and progesterone/estradiol ratio (P4/E2) on pregnancy outcome in IVF/intracytoplasmic sperm injection (ICSI) cycles with long agonist protocol. SETTING AND DESIGN: Retrospective, single center, cohort study. MATERIALS AND METHODS: A review of complete data of 544 women undergoing fresh IVF/ICSI cycles (539 cycles) with long agonist protocol from January 2012 to February 2014 was done. Data were stratified into Three groups according to the number of oocytes retrieved: low (≤4 oocytes obtained), intermediate (5-19 oocytes obtained), and high ovarian response (≥20 oocytes obtained). STATISTICAL ANALYSIS: Fishers exact test/Chi-square was carried for comparing categorical data. Receiver operating characteristics analysis was performed to determine the cut-off value for P4 and P4/E2 detrimental for pregnancy. RESULTS: A negative association was observed between pregnancy rate (PR) and serum P4 and P4/E2 levels with no effect on fertilization and cleavage rate. The overall cut-off value of serum P4 and P4/E2 ratio detrimental for pregnancy was found to be 1.075 and ≥0.35, respectively. Different P4 threshold according to the ovarian responders were calculated, 1.075 for intermediate and 1.275 for high responders. Serum E2 levels were not found to be significantly associated with PR. CONCLUSION: Serum P4 levels and P4/E2 ratio are a significant predictor for pregnancy outcome without affecting cleavage and fertilization rate while serum estradiol levels do not seem to affect PR.

Progesterone/Estradiol Ratio as a Predictor in the ART Cycles with Premature Progesterone Elevation on the Day of hCG Trigger.

BACKGROUND: The purpose of the study was to evaluate the role of Progesterone/ Estradiol (P4/E2) ratio as a predictive tool for clinical pregnancy in ART cycles with a premature progesterone rise of >1.5 ng/ml on the day of human chorionic gonadotropin (hCG) trigger. METHODS: Retrospective analysis was done on 569 fresh embryo transfer cycles from January 2011 to December 2012 at the infertility unit of a tertiary care hospital. Age, BMI, number of cycles and number of clinical pregnancies have been considered. RESULTS: The overall clinical pregnancy rate per embryo transfer was 42.8% (244/569). The clinical pregnancy rate in the 36 cycles with progesterone (P4) level >1.5 ng/ml was significantly lower than the 533 cycles with normal p4 ≤1.5 ng/ml (22.2% vs. 44.2%; p=0.0092). The 36 cycles with progesterone level >1.5 ng/ml were divided into subgroups of P4/E2 >1 (n=20) and P4/E2 ≤1 (n=16). The 20 cycles with P4/E2 >1 and P4 >1.5 ng/ml had a significantly lower pregnancy rate than the cycles with P4 ≤1.5 ng/ml (15% vs. 42.8%; p=0.0103). The 15 cycles with P4/E2 ≤1 and P4 >1.5 ng/ml had a similar pregnancy rate as the cycles with P4 ≤1.5 ng/ml. CONCLUSION: A premature progesterone elevation in ART cycles is possibly associated with lower clinical pregnancy rates; this adverse impact of elevated progesterone seems to be limited mainly to a subgroup with an elevated P4/E2 ratio >1.