Abstract

Abstract Study question Is there a ceiling effect of high serum progesterone levels on day of embryo transfer for pregnancy outcomes in patients undergoing artificial frozen-thawed blastocyst transfer? Summary answer There is no ceiling effect of high serum progesterone levels on day of embryo transfer(>40 ng/mL)for pregnancy outcomes in patients undergoing artificial frozen-thawed blastocyst transfer. What is known already In recent studies, 10 ng/mL was usually used as the lower threshold value for serum progesterone (P4) level on the day of embryo transfer in patients undergoing artificial frozen-thawed blastocyst transfers and pregnancy outcomes were compared between patients with P4 levels above and below this threshold. The main reason for choosing this threshold in the studies is that it reflects the healthy corpus luteum function. Although many studies have investigated the lower threshold value, there is paucity of data on the high threshold value that can indicate the possible ceiling effect of P4 in the literature. Study design, size, duration This was a retrospective cohort study including 595 patients undergoing artificial frozen-thawed blastocyst transfer between 2017 to 2021. In order to eliminate the age-related bias, only patients performed euploid embryo transfer according to preimplantation genetic testing for aneuploidy from patients above aged 35 years were included. Participants/materials, setting, methods When we evaluated the percentiles of according to the progesterone levels,40.6 ng/ml corresponded to 90th percentile and 23.9 ng/ml corresponded to 50th percentile. Based on this finding, rounding up the numbers, we determined the progesterone levels cut-off as < 20ng/mL,n=220(37.0%);20-40ng/mL,n=312(52.4%) and ≥40ng/mL,n=63(10.6%). The main outcome measure was pregnancy outcomes as clinical pregnancy and live birth rate. We compared pregnancy outcomes according to age, BMI, blastocyst expansion, trophectoderm and inner cell mass grade and progesterone cut-off levels . Main results and the role of chance The median age of the patients was 31 (Range 20-46) and the mean body mass index (BMI) of the patients was 24.5±4.0 kg/m2. The overall clinical pregnancy rate and live birth rate were 61.8% (368/595) and 52.9% (315/595), respectively. Patients were subdivided into two different groups according to clinical pregnancy and live birth rate outcomes as follows; positive and negative. Age and BMI of patients were comparable between groups. Blastocyst morphology grade as expansion, trophectoderm and inner cell mass grade are statistically significantly associated with clinical pregnancy (p<.001 for all) and progesterone level between 20-40ng/mL is associated with higher clinical pregnancy rate (p:0.043). In multivariate analysis; only blastocyst expansion and inner cell mass grade were the independently and significantly factors that are associated with clinical pregnancy rate (p:0.011, OR: 1.6, CI95%: 1.13-2.39 and p:0.007, OR: 1.65, CI95%: 1.14-2.39, respectively). Progesterone level and trophectoderm grade were not fount statistically significant (p: 0.310 and p:0.489, respectively). In evaluation of the association between factors and live birth rate, only blastocyst expansion grade equal or over 4 and trophectoderm grade A or B were associated with statistically significant live birth rates. Limitations, reasons for caution The main limitations of current study were the retrospective design and the limited sample size of the ≥40 ng/mL cohort of serum progesterone levels. Wider implications of the findings According to this data, we speculated that if the serum P4 level is above 40 ng/mL on the day of embryo transfer in patients undergoing artificial frozen-thawed blastocyst transfer, there is no need to reduce the dose of progesterone used. Trial registration number N/A

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