P–404 Low serum progesterone on the day of frozen blastocyst transfer is associated with a diminished ongoing pregnancy rate in hormonal replacement therapy cycles

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Maignien ◽  
B Mathilde ◽  
B Valérie ◽  
C Ahmed ◽  
C Charles ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Frozen Embryo Transfer ◽  
Blastocyst Transfer ◽  
Progesterone Level ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate ◽  
Serum Progesterone ◽  
Hormonal Replacement

Abstract Study question Is there a relationship between progesterone levels on the day of frozen blastocyst transfer and ongoing pregnancy rate (OPR), in hormonal replacement therapy (HRT) cycles? Summary answer Women undergoing HRT-frozen embryo transfer with progesterone levels≤9.76ng/ml on the day of blastocyst transfer had a significantly lower OPR than those with progesterone levels>9.76 ng/ml. What is known already The importance of serum progesterone levels around the time of frozen embryo transfer (FET) is a burning issue, in view of the growing number of FET worldwide. However, the optimal range of serum progesterone levels is not clearly determined and discrepancies arise from the current literature. Study design, size, duration: Observational cohort study with 915 patients undergoing HRT-FET at a tertiary care university hospital, between January 2019 and March 2020. Participants/materials, setting, methods Patients undergoing single autologous blastocyst FET under HRT using exogenous estradiol and vaginal micronized progesterone for endometrial preparation. Women were only included once during the study period. The serum progesterone level was measured in the morning of the FET, in a single laboratory. The primary endpoint was OPR beyond pregnancy week 12. Statistical analysis was conducted using univariate and multivariate logistic regression models. Main results and the role of chance Mean serum progesterone level on the day of FET was 12.90 ± 4.89 ng/ml). The OPR was 35.5% (325/915) in the overall population. Patients with a progesterone level ≤ 25th percentile (≤9.76ng/ml) had a significantly lower OPR and a higher miscarriage rate (MR) compared with women with progesterone level over Centile 25 (29.6% versus 37.4%; p = 0.033 and 34.8% versus 21.3%; p = 0.008, respectively). After adjustment for the potential confounders in a multivariate analysis, a serum progesterone level ≤ 9.76 ng/ml on the day of FETand FET of a Day 6-blastocyst (versus Day 5-blastocyst) were found as independent risks factor of lower OPR. Limitations, reasons for caution The main limitation of our study is linked to its observational design. Extrapolation of our results to other laboratories, or other routes and/or doses of administering progesterone also needs to be validated. Wider implications of the findings: This study suggests that a minimum serum progesterone level is needed to optimize reproductive outcomes in autologous blastocyst FET, in HRT-cycles. Further studies are needed to evaluate if modifications of progesterone routes and/or doses may improve pregnancy chances, in an approach to individualize the management of ART patients. Trial registration number NA

Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospective cohort study

2021 ◽  
Author(s):  
Manuel Álvarez ◽  
Sofía Gaggiotti-Marre ◽  
Francisca Martínez ◽  
Lluc Coll ◽  
Sandra García ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Luteal Phase ◽  
Frozen Embryo Transfer ◽  
Ongoing Pregnancy ◽  
Serum Progesterone ◽  
Endometrial Preparation ◽  
Group 2 ◽  
Group 1

Abstract STUDY QUESTION Does an individualised luteal phase support (iLPS), according to serum progesterone (P4) level the day prior to euploid frozen embryo transfer (FET), improve pregnancy outcomes when started on the day previous to embryo transfer? SUMMARY ANSWER Patients with low serum P4 the day prior to euploid FET can benefit from the addition of daily subcutaneous P4 injections (Psc), when started the day prior to FET, and achieve similar reproductive outcomes compared to those with initial adequate P4 levels. WHAT IS KNOWN ALREADY The ratio between FET/IVF has spectacularly increased in the last years mainly thanks to the pursuit of an ovarian hyperstimulation syndrome free clinic and the development of preimplantation genetic testing (PGT). There is currently a big concern regarding the endometrial preparation for FET, especially in relation to serum P4 levels around the time of embryo transfer. Several studies have described impaired pregnancy outcomes in those patients with low P4 levels around the time of FET, considering 10 ng/ml as one of the most accepted reference values. To date, no prospective study has been designed to compare the reproductive outcomes between patients with adequate P4 the day previous to euploid FET and those with low, but restored P4 levels on the transfer day after iLPS through daily Psc started on the day previous to FET. STUDY DESIGN, SIZE, DURATION A prospective observational study was conducted at a university-affiliated fertility centre between November 2018 and January 2020 in patients undergoing PGT for aneuploidies (PGT-A) IVF cycles and a subsequent FET under hormone replacement treatment (HRT). A total of 574 cycles (453 patients) were analysed: 348 cycles (leading to 342 euploid FET) with adequate P4 on the day previous to FET, and 226 cycles (leading to 220 euploid FET) under iLPS after low P4 on the previous day to FET, but restored P4 levels on the transfer day. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall we included 574 HRT FET cycles (453 patients). Standard HRT was used for endometrial preparation. P4 levels were measured the day previous to euploid FET. P4 > 10.6 ng/ml was considered as adequate and euploid FET was performed on the following day (FET Group 1). P4 < 10.6 ng/ml was considered as low, iLPS was added in the form of daily Psc injections, and a new P4 analysis was performed on the following day. FET was only performed on the same day when a restored P4 > 10.6 ng/ml was achieved (98.2% of cases) (FET Group 2). MAIN RESULTS AND THE ROLE OF CHANCE Patient’s demographics and cycle parameters were comparable between both euploid FET groups (FET Group 1 and FET Group 2) in terms of age, weight, oestradiol and P4 levels and number of embryos transferred. No statistically significant differences were found in terms of clinical pregnancy rate (56.4% vs 59.1%: rate difference (RD) −2.7%, 95% CI [−11.4; 6.0]), ongoing pregnancy rate (49.4% vs 53.6%: RD −4.2%, 95% CI [−13.1; 4.7]) or live birth rate (49.1% vs 52.3%: RD −3.2%, 95% CI [−12; 5.7]). No significant differences were also found according to miscarriage rate (12.4% vs 9.2%: RD 3.2%, 95% CI [−4.3; 10.7]). LIMITATIONS, REASONS FOR CAUTION Only iLPS through daily Psc was evaluated. The time for Psc injection was not stated and no serum P4 determinations were performed once the pregnancy was achieved. WIDER IMPLICATIONS OF THE FINDINGS Our study provides information regarding an ‘opportunity window’ for improved ongoing pregnancy rates and miscarriage rates through a daily Psc injection in cases of inadequate P4 levels the day previous to FET (P4 < 10.6 ng/ml) and restored values the day of FET (P4 > 10.6 ng/ml). Only euploid FET under HRT were considered, avoiding one of the main reasons of miscarriage and implantation failure and overcoming confounding factors such as female age, embryo quality or ovarian stimulation protocols. STUDY FUNDING/COMPETING INTEREST(S) No external funding was received. B.C. reports personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, IBSA and Gedeon Richter outside the submitted work. N.P. reports grants and personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, Theramex and Besins International and personal fees from IBSA and Gedeon Richter outside the submitted work. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER NCT03740568.

scholarly journals Endometrial compaction and serum progesterone measurements at the day of embryo transfer cannot predict pregnancy outcomes in frozen-thaw embryo transfer cycles

2021 ◽  
Vol 12 (1) ◽  
pp. 407-415
Author(s):  
Dalal M. Al Jarrah ◽  
Manal Taha Al Obaidi ◽  
Itlal J. AL Asadi
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Endometrial Thickness ◽  
Transvaginal Ultrasound ◽  
P Value ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate ◽  
Serum Progesterone ◽  
The Impact

Endometrial receptivity plays a basic role in successful embryo implantation and pregnancy outcomes and can be assessed by many of non-invasive markers. Our study evaluated the impact of two of these markers specifically serum progesterone and endometrial thickness at embryo transfer day in prediction pregnancy outcomes on (60) patients attempting medicated frozen embryo transfer (FET) cycles. All patients were received sequential estrogen & progesterone medications for endometrial preparation then submitted to measurements of endometrial thickness (EMT) by transvaginal-ultrasound (TV-US) & serums progesterone (P) analysis at the embryo transfer day, thereafter day 3 verified-thawed embryos grades (A±B) were transferred. Compacted (decreased) EMT was seen in 48.3% of patients with higher pregnancy rate (PR) of 58.6%t than non-compacted EMT (no change or increased) which was seen in 51.7% of patients with (PR) of 29.0%, (P value=0.021). However ongoing pregnancy rate (Ong PR) not differed significantly between both groups (44.8% in compacted vs 25.8% in non-compacted, P value=0.053), also the means of serum P not differed between pregnant and non-pregnant patients (P value=0.374). ROC curves for Ong PR prediction in relations to endometrial compaction & serum progesterone at embryo transfer day were poor (AUC= 0.630, & AUC=0.576, respectively). This study suggested that endometrial compaction or serum P levels measurements at embryo transfer day were poor predictors for ongoing pregnancy where any kind of EMT changes (decreased or not) seen after P administration not significantly affect pregnancy outcomes in frozen-thaw cycles of cleavage stage embryos transfer.

O-200 Frozen embryo transfer: Miscarriage rates depending on the starting day of intramuscular progesterone

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N Kalhorpour ◽  
B Martin ◽  
O Kulski ◽  
J M Mayenga ◽  
I Grefenstette ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Live Birth ◽  
Frozen Embryo Transfer ◽  
Ongoing Pregnancy ◽  
Miscarriage Rate ◽  
Ongoing Pregnancy Rate ◽  
Group A ◽  
Group B ◽  
Day Of Embryo Transfer

Abstract Study question Objective was to assess whether adjusting starting day of intramuscular progesterone the day of vaginal supplementation versus day of embryo transfer or later, might affect the outcome of the cycle. Summary answer additional injection of intramuscular progesterone the day of progesterone initiation or later, is not likely to be more effective on live birth and miscarriage rates. What is known already There is no consensus on the most effective method of endometrium preparation prior to FET. However, many studies report that high serum progesterone concentration during the implantation period is associated with optimal live birth rates. Adjusting progesterone treatment the day of embryo transfer seems to be too late and ineffective for rescuing low progesterone levels and should be done before. Study design, size, duration In this single center prospective study from October 2019 to november 2020, 239 patients undergoing hormonal replacement therapy protocol for frozen embryo transfer were randomly divided into two groups: additional injection of intramuscular progesterone the day of progesterone initiation or intramuscular progesterone the day of embryo transfer. We compare these results to our previous protocol beginning intramuscular progesterone day 22 of the treatment. Participants/materials, setting, methods Our frozen embryo transfer protocol consists to initiate GnRH agonist the day 1 of the cycle. After 14 days of estrogens, we introduce vaginal progesterone, prior to embryo transfer. Patients in group A received an additional injection of intramuscular progesterone the day of progesterone initiation. The group B received intramuscular progesterone the day of embryo transfer. For both, intramuscular injection of progesterone was followed every 3 days. Main results and the role of chance 239 patients were enrolled in this study, 125 in the group A and 114 in the group B. The ongoing pregnancy rate in the group A was 26.4 % and miscarriage rate 7.2%, not statistically different from ongoing pregnancy rate and miscarriage rate of women in the group B (22.81 %, p = 0.66/ 6.14%, p = 0.8). The ongoing pregnancy rate in the group D22 was 24.89 % et miscarriage rate 7.2%, not statistically different from ongoing pregnancy rate of women in the group A and B (p = 0.78 and p = 0.31). Limitations, reasons for caution The main limitation of our study is the lack of randomization for the group with additional progesterone IM on day 22. The study is actually followed to enroll more patients in 3 different groups. Wider implications of the findings This study tries to determine optimal adaptive management of hormonal replacement treatment for embryo transfer in patients with potential low progesterone values. Trial registration number no applicable

Progesterone levels on the human chorionic gonadotropin trigger day affect the pregnancy rates for embryos transferred at different stages of development in both general and selected IVF/ICSI populations

2020 ◽  
Author(s):  
Philippe Merviel ◽  
Sarah Bouée ◽  
Anne-Solenn Jacamon ◽  
Jean-Jacques Chabaud ◽  
Marie-Thérèse Le Martelot ◽  
...  
Keyword(s):  
General Population ◽  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Predictive Factors ◽  
Pregnancy Rates ◽  
Clinical Pregnancy ◽  
Clinical Pregnancy Rate ◽  
Blastocyst Transfer ◽  
Progesterone Level ◽  
Serum Progesterone

Abstract Background Two meta-analyses have shown that pregnancy and birth rates are significantly higher after blastocyst transfer than after cleaved embryo transfer. Other studies have revealed that a serum progesterone level > 1.5 ng/ml on the trigger day is responsible for premature luteinization and is associated with a low pregnancy rate. The objectives of the present study were to determine whether blastocyst transfer gave higher pregnancy rates than cleaved embryo transfer at day 3 in both the general and selected IVF/ICSI populations, and whether the serum progesterone level influenced the pregnancy rate. Method : We studied IVF/ICSI cycles with GnRH antagonist - FSH/hMG protocols in a general population (n = 1210) and a selected “top cycle” population (n = 677), after blastocyst transfer on D5 or cleaved embryo transfer on D3. The selected cycles had to meet the following criteria: female age < 35, first or second cycle, and one or two embryos transferred. We recorded predictive factors for pregnancy and calculated the serum progesterone to oocyte ratio (P/Ooc), the serum progesterone to serum estradiol ratio (P/E2), and the serum progesterone to follicle (> 14 mm) index (PFI). Results In the general population, the clinical pregnancy rate was significantly higher after blastocyst transfer (33.3%) than after cleaved embryo transfer (25.3%; p < 0.01). The differences between blastocyst and embryo transfer groups were not significant in the selected population (respectively 35.7% vs. 35.8% for the clinical pregnancy rate). The only predictive factors common to the general and selected populations were the serum progesterone levels on the eve of the trigger day and on the day itself, which were significantly lower in the subgroups of women who became pregnant (p < 0.01). We found a serum progesterone threshold of 0.9 ng/ml, as also reported by other studies. The P/Ooc ratio and the PFI appear to have predictive value for cleaved embryos transfers. Conclusions Blastocyst transfers were associated with higher clinical pregnancy rate than cleaved embryo transfers in a general population but not in a selected population. The serum progesterone levels on the eve of the trigger day and on the day itself predicted the likelihood of pregnancy.

scholarly journals Does serum progesterone level impact the ongoing pregnancy rate in frozen embryo transfer under artificial preparation with vaginal progesterone? Study protocol for a randomized controlled trial

Trials ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Lin Haiyan ◽  
Yang Gang ◽  
Li Yu ◽  
Li Lin ◽  
Chen Xiaoli ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Clinical Pregnancy ◽  
Frozen Embryo Transfer ◽  
Progesterone Level ◽  
Sufficient Evidence ◽  
Ongoing Pregnancy ◽  
Serum Progesterone ◽  
Randomized Controlled ◽  
Link Type ◽  
Low Serum

Abstract Background In previous retrospective studies, low serum progesterone level on the embryo transfer day is associated with lower clinical pregnancy and ongoing pregnancy rates. Whether adding progesterone in low serum progesterone patients can rescue the outcome, there is no sufficient evidence from randomized controlled studies. Methods This trial is a clinical randomized controlled study (high serum progesterone vs low serum progesterone 1:1, 1:1 randomization ratio of intervention vs the control group with low serum progesterone). The eligible hormone replacement therapy—frozen embryo transfer (HRT-FET) cycles, will be recruited and randomly assigned to two parallel groups when serum progesterone is < 7.24μg/l on the day of embryo transfer for D3. The intervention group will be extrally given intramuscular progesterone 40 mg per day from D3 to 8 weeks of gestation if clinical pregnancy. The primary outcome is the ongoing pregnancy (beyond 12 weeks of gestation) rate. Discussion The findings of this study will provide strong evidence for whether the progesterone addition from the D3 in low serum progesterone patients can improve the outcome in the HRT-FET cycle. Trial registration ClinicalTrials.govNCT04248309. Registered on January 28, 2020

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