Serum progesterone level and ongoing pregnancy rate following frozen-thawed embryo transfer after artificial endometrial preparation: a monocentric retrospective study

2020 ◽  
Vol 49 (10) ◽  
pp. 101828
Author(s):  
M. Commissaire ◽  
S. Epelboin ◽  
M. Vigan ◽  
S. Tubiana ◽  
M.A. Llabador ◽  
...  
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P K Sim ◽  
P Nadkarni

Abstract Study question Between spontaneous ovulation (SPO) and induced ovulation (INO) comparing clinical pregnancy rate and ongoing pregnancy rate for frozen-thawed embryo transfer (FET) cycle, which is better? Summary answer Both spontaneous ovulation and induced ovulation protocols showed no significant difference in clinical pregnancy rates and ongoing pregnancy rates. What is known already Recent practice worldwide is moving towards elective freezing of all embryos and subsequent frozen-thawed transfer, both for a perceived higher pregnancy rate as well as the significant reduction of ovarian hyperstimulation. The timing of FET can be determined by either detecting the spontaneous Luteinizing Hormone surge (SPO group) or by the administration of hCG (INO group). There is still an ongoing debate to determine which is the best protocol for frozen-thawed embryo transfer in the non-hormone replacement therapy (non-HRT) cycle. Study design, size, duration This retrospective study included 500 FET cycles for patients who had regular menses between June 2017 and June 2020. The FET cycles were grouped by type as follows: SPO (n = 281) and INO (n = 219). The primary outcome was the clinical pregnancy rate and the secondary outcome was ongoing pregnancy rate. Ongoing pregnancy is defined as a viable intrauterine pregnancy at 12 weeks of gestation confirmed on an ultrasound scan. Participants/materials, setting, methods This study was conducted in a single IVF centre. Vitrification was used as the cryopreservation method. To standardize outcome measures, only patients having single blastocyst transfer and aged under 38 years old were included. The average age of the patient was 32.9. Gamete donation, embryo donation, pre-implantation testing and assisted hatching cycles were also excluded from the analysis. Categorical data were analysed using Chi-square test SPSS version 25. Main results and the role of chance Clinical pregnancy rate for SPO group was 54.8% (154/281) versus 52.9% (116/219) in INO group. Even though clinical pregnancy rate was higher in SPO group as compared to INO group, it did not reach significance level (ꭓ2 = 0.17, p = 0.68). As all patients had single blastocyst transferred, the implantation rate was the same as clinical pregnancy rate. Ongoing pregnancy rate was also found higher in SPO group as compared to INO group (135/281, 48.0% and 97/219, 44.3% respectively) but again failed to reach significance level (ꭓ2 = 0.70, p = 0.40). Limitations, reasons for caution The retrospective nature of the study and therefore, the analysis was not adjusted for confounding factors such as blastocyst grading, etiology of infertility, and ethnicity of patients. Wider implications of the findings: In natural cycle, both spontaneous ovulation and induced ovulation protocols had the same pregnancy outcomes for frozen-thawed embryo transfer. However, induced ovulation can facilitate in scheduling FET timing to avoid weekends and public holidays, if necessary. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Maignien ◽  
B Mathilde ◽  
B Valérie ◽  
C Ahmed ◽  
C Charles ◽  
...  

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


2021 ◽  
Author(s):  
Manuel Álvarez ◽  
Sofía Gaggiotti-Marre ◽  
Francisca Martínez ◽  
Lluc Coll ◽  
Sandra García ◽  
...  

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.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Cedri. . Durnerin ◽  
M Peigné ◽  
J Labrosse ◽  
M Guerout ◽  
C Vinolas ◽  
...  

Abstract Study question Does systematic dydrogesterone supplementation in artificial cycles (AC) for frozen-thawed embryo transfer (FET) during Covid–19 pandemic modify outcomes compared to prior individualized supplementation adjusted on serum progesterone (P) levels ? Summary answer Systematic dydrogesterone supplementation in AC for FET is associated with similar outcomes compared to prior individualized supplementation in patients with low P levels. What is known already In AC for FET using vaginal P for endometrial preparation, low serum P levels following P administration have been associated with decreased pregnancy and live birth rates. This deleterious effect can be overcome by addition of other routes of P administration. We obtained effective results by adding dydrogesterone to vaginal P and postponing FET by one day in patients with low P levels. However, in order to limit patient monitoring visits and to schedule better FET activity during Covid–19 pandemic, we implemented a systematic dydrogesterone supplementation without luteal P measurement in artificial FET cycles. Study design, size, duration This retrospective study aimed to analyse outcomes of 394 FET after 2 different protocols of artificial endometrial preparation. From September 2019 to Covid–19 lockdown on 15th March 2020, patients had serum P level measured on D1 of vaginal P administration. When P levels were < 11 ng/ml, dydrogesterone supplementation was administered and FET was postponed by one day. From May to December 2020, no P measurement was performed and dydrogesterone supplementation was systematically used. Participants/materials, setting, methods In our university hospital, endometrial preparation was performed using sequential administration of vaginal estradiol until endometrial thickness reached >7 mm, followed by transdermal estradiol combined with 800 mg/day vaginal micronized P started in the evening (D0). Oral dydrogesterone supplementation (30 mg/day) was started concomitantly to vaginal P in all patients during Covid–19 pandemic and only after D1 P measurement followed by one day FET postponement in patients with P levels <11 ng/ml before the lockdown. Main results and the role of chance During the Covid–19 pandemic, 198 FET were performed on D2, D3 or D5 of P administration with dydrogesterone supplementation depending on embryo stage at cryopreservation. Concerning the 196 FET before lockdown, 124 (63%) were performed after dydrogesterone addition from D1 onwards and postponement by one day in patients with serum P levels <11 ng/ml at D1 while 72 were performed in phase following introduction of vaginal P without dydrogesterone supplementation in patients with P > 11 ng/ml. Characteristics of patients in the 2 time periods were similar for age (34.5 + 5 vs 34.1 + 4.8 years), endometrial thickness prior to P introduction (9.9 + 2.1 vs 9.9 + 2.2 mm), number of transferred embryos (1.3 + 0.5 vs 1.4 + 0.5) , embryo transfer stage (D2/D3/blastocyst: 8/16/76% vs 3/18/79%). No significant difference was observed between both time periods [nor between “dydrogesterone addition and postponement by 1 day” and “in phase” FET before lockdown] in terms of positive pregnancy test (39.4% vs 39.3% [44% vs 30.5%]), heartbeat activity at 8 weeks (29.3% vs 28% [29% vs 26.4%]) and ongoing pregnancy rates at 12 weeks (30.7% but truncated at end of October 2020 vs 25.5% [26.6% vs 23.6%]). Limitations, reasons for caution Full results of the Covid–19 period will be further provided concerning ongoing pregnancy rates as well as comparison of live birth rates and obstetrical and neonatal outcomes. Wider implications of the findings: These results suggest that systematic dydrogesterone supplementation is as effective as individualized supplementation according to serum P levels following administration of vaginal P. This strategy enabled us to schedule easier FET and limit patient visits for monitoring while maintaining optimal results for FET in AC during the Covid–19 pandemic. Trial registration number Not applicable


Sign in / Sign up

Export Citation Format

Share Document