P–605 Low serum progesterone on the day of frozen embryo transfer after artificial endometrial preparation: exploring the clinical impact of “rescue” strategies

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Herencia ◽  
J Llácer ◽  
J A Ortiz ◽  
J C Castillo ◽  
C Gavilán ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Embryo Transfer ◽  
Pregnancy Rates ◽  
Frozen Embryo Transfer ◽  
Control Group ◽  
Ongoing Pregnancy ◽  
Serum Progesterone ◽  
Endometrial Preparation ◽  
Vaginal Progesterone ◽  
Low Serum

Abstract Study question Can we rescue treatments with low progesterone (PG) levels the day of frozen embryo transfer (FET) by adding subcutaneous progesterone? Summary answer After receiving additional supplementation with subcutaneous progesterone, women with low serum progesterone on cryotransfer day, have similar ongoing pregnancy rates as women with normal levels. What is known already Micronized vaginal progesterone fails to achieve optimal serum levels in up to 30% of patients receiving frozen embryos under artificial cycles (AC) despite the administration of 400 mg twice daily. Cancelling the thawing process and restarting a new treatment is a very disappointing option for patients and doctors. An alternative strategy is to administrate additional progesterone subcutaneously. The efficacy of the additional administration of subcutaneous progesterone as a “rescue” strategy in terms of clinical outcomes remains to be validated. Study design, size, duration We included 356 FET performed at Instituto Bernabeu between January 2019 - August 2020 in a retrospective case-control study. Groups were established according to PG levels on the day of the embryo transfer. The Control Group included: patients with optimal progesterone levels (≥8.8 ng ml); while the Rescue Group included those with suboptimal progesterone levels (<8.8 ng ml). Participants/materials, setting, methods All patients performed frozen embryo transfer after artificial endometrial preparation. All embryo transfers were performed at blastocyst stage after 5 days of progesterone administration. Progesterone levels were assessed the day of the embryo transfer by an electrochemiluminescence immunoassay. Samples were obtained 2–5 hours after the last vaginal progesterone administration. Primary outcome was Ongoing Pregnancy Rates (OPR). Secondary outcomes were pregnancy rates (PR), miscarriage rates (MR) and biochemical miscarriage (BM). Main results and the role of chance 301 patients were included in the Control Group and 55 in the Rescue Group. No significant differences were found between both groups. OPR rate was 34.7% for patients in the control group versus 26.4% in the rescue group (p = 0.240) PR was 52.5% for patients with optimal PG levels vs 54.5% when PG levels were below 8.8 ng/mL. Both BM and MR tend to be higher in women who had low serum PG: BM (21.4% vs 15.5%) and MR (28.6% vs 18.1%), without reaching significant statistical difference. In addition, we analyzed data from a sub-group of patients who received extra subcutaneous progesterone (based on cliniciańs decision), despite having normal serum PG levels. No differences in clinical outcomes between these groups were observed either. OPR was 29%, vs 35.4% (p = 0.241), PR was 51.8% vs 53.7%; BM was 16.7% vs 16.3% and MR was 26.9% vs 17.1% between women who received an extra subcutaneous PG dose versus women who did not, respectively. Weight and BMI distribution were homogeneous across groups. A discreet difference was observed in age distribution (control group mean age 41.6 years vs. 39.7 years in the rescue group). Limitations, reasons for caution The retrospective collection of data and a limited sample size constitutes the main limitations of the study. Significant statistical differences were not found between groups but still differences might be clinically relevant. Larger studies are needed to reach robust conclusions on the strategy. Wider implications of the findings: In AC cycles, when supplemented with additional subcutaneous progesterone, women showing low serum progesterone on cryotransfer day may expect similar clinical outcomes as women with normal levels. Pending on confirmatory studies, this strategy could consider as an alternative to cycle cancellation. Trial registration number Not applicable

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.

P–411 Does subcutaneous progesterone (SC-P) administration eliminate the necessity of serum progesterone level monitoring in frozen embryo transfer (FET) cycles?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F K Boynukalin ◽  
R Abalı ◽  
M Gultomruk ◽  
B Demir ◽  
Z Yarkiner ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Clinical Outcomes ◽  
Embryo Transfer ◽  
Endometrial Thickness ◽  
Hormone Replacement ◽  
Pregnancy Rates ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate ◽  
Serum Progesterone ◽  
Female Age

Abstract Study question Does SC-P provide similar ongoing pregnancy rates (OPRs) as intramuscular progesterone(IM-P) in hormone replacement therapy (HRT)-FET cycles and do serum progesterone (P) levels on FET day effect on pregnancy outcome? Summary answer: SC-P administration had similar OPR compared to IM-P in HRT-FET cycles. In SC-P group embryo transfer(ET) day P found to be insignificant factor for outcome. What is known already Different P routes can be used in HRT-FET cycles such as vaginal P, IM-P and recently SC-P. Only retrospective studies evaluated the comparison of SC-P with other routes in HRT-FET cycles. Here, we assessed prospectively whether SC-P is effective for HRT-FET cycles. Previous studies reported that serum P levels on ET day after vaginal P administration clinical outcomes were closely correlated. The correlation between serum P after IM-P administration and clinical outcomes were conflicting. In addition, there is lack of data on the serum P levels after SC-P administration. Serum P levels on ET day were evaluated in this study. Study design, size, duration This prospective cohort study was performed between July 1-October 31 2020, enrolled 224 patients scheduled for HRT-FET cycles with SC-P(25 mg twice daily) or IM-P(50 mg once daily). The route of P was decided according to the patient’s eligibility to hospital. First FET cycle was included after freeze-all cycles for each patients. Female age>35, PGT-A cycles, cleavage ET, >1 ET, patients with uterine pathology and hydrosalpinx, FET with surplus embryos, endometrial thickness<7mm were excluded. Participants/materials, setting, methods Female age ≤ 35 years old with a triple-layer endometrium >7 mm underwent transfer of single blastocysts after the first ET after freeze-all cycles. The indications for freeze-all were ovarian hyperstimuation syndrome and trigger day P level>1.5 ng/ml. 224 patients were eligible for study; 133 in SC-P group and 91 in IM-P group.The primary endpoint was the ongoing pregnancy rate (OPR) beyond pregnancy week 12. Main results and the role of chance The demographic, cycle, embryologic characteristics were similar between groups. The median circulating P levels on the day of ET were 19.92(15.195–27.255)ng/
ml and 21(16.48–28)ng/ml in the SC-P and IM-P groups,(p = 0.786). The clinical pregnancy rates [86/133(64.7%) vs 57/91(62.6%);p=0.757], miscarriage rates [21/86(24.4%) vs 10/57(17.5%) ;p=0.329], and OPR [65/133 (48.9%) vs 47/91(51.6%); p = 0.683] were comparable between the SC-P and IM-P. Binary logistic regression was performed for ongoing pregnancy as the dependent factor blastocyst morphology was found to be the only significant independent prognostic factor (p = 0.006), whereas the route of P was insignificant. In the SC-P and IM-P 
groups, the effect of ET day P levels were divided into quartiles(Q) to evaluate the effect on ongoing pregnancy. In SC-P group OPR were similar in four Q [Q1:33.3%(11/33),Q2:50%(17/34),Q3:60.6%(20/33),Q4:51.5%(17/33) (p = 0.1)].For IM-P group; Q1 had a significantly reduced OPR than Q2, Q3, Q4. [26.1%(6/23),65.2%(15/23),54.5%(12/22) and 60.9%(14/23), p = 0.031]. Logistic regression analysis for OP was performed separately in SC-P group and IM-P group. Although in SC-P group, ET day P levels was not found to be a significant factor, in IM-P ET day P level was found to be an independent factor for OP in IM-P group (Q1vs Q2+Q3+Q4; OR: 8,178 95% CI: [1.387–48.223] p:0.02). . Limitations, reasons for caution Although this study has the advantage of being prospective and in a homogenous study population, randomized controlled trials are warranted to evaluate the effectiveness of SC-P to other routes of P. Extrapolation to unselected populations of this study is needed. Wider implications of the findings: Assignment of threshold of serum P on the day of ET for HRT-FET cycles to optimize outcomes is critical for every route of P. Regarding these results, individual luteal phase for HRT-FET cycles can improve IVF outcome. Trial registration number None

P–630 Progesterone levels using pessaries of 400 mg of vaginal progesterone (Cyclogest®) in artificial cycles for frozen embryo transfer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Llacer ◽  
A Pitas ◽  
J A Ortiz ◽  
C Gavilán ◽  
A Herencia ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Embryo Transfer ◽  
Pregnancy Rates ◽  
Frozen Embryo Transfer ◽  
The Body ◽  
Patient Comfort ◽  
Medical Decision ◽  
Endometrial Preparation ◽  
Group A ◽  
Group B

Abstract Study question Does the use of pessaries of 400 mg of micronized progesterone provide comparable results as pessaries of 200 mg x2, in terms of progesterone levels? Summary answer The administration of pessaries of Cyclogest® 400 mg reduces the probability of presenting suboptimal level of progesterone on the day of the embryo transfer. What is known already The endometrial preparation for frozen embryo transfer (FET) in Artificial Cycle (AC) with vaginally-administered progesterone, is one of the most common IVF procedures nowadays. Now, it has been shown that suboptimal progesterone levels on the day of the embryo transfer compromise the results of FET treatments. Recently, a new preparation of 400 mg vaginal pessaries has been introduced in the market of European countries. Efficacy of this new preparation has been studied in “fresh” IVF cycles but we lack the comparative studies in AC making it necessary to further investigate this area. Study design, size, duration Non-inferiority retrospective case-control trial based on 347 embryo transfer treatments with endometrial preparation in AC carried out at Instituto Bernabeu between January 2019 and July 2020. 153 patients received 1 pessary of 400 mg every 12 hours (group A) and 194 received 2 pessaries of 200 mg every 12 hours (group B). Sampled size calculation resulted in 182 patients required to detect a minimum difference of 2 ng/ml so sample was powered for the purpose. Participants/materials, setting, methods Patients receiving embryos in AC preparation were included. All embryo transfers were performed at blastocyst stage after 5 days of progesterone administration. Progesterone levels were assessed the day of the embryo transfer by an electrochemiluminescence immunoassay.Primary outcome was the incidence of suboptimal progesterone levels according with the cutoff value stablished in the literature at 8.8 ng/mL. Secondary outcomes were pregnancy rates (PR), clinical pregnancy rates (CPR), ongoing pregnancy rates (OPR) and miscarriage rates (MR). Main results and the role of chance Incidence of suboptimal levels of progesterone was significantly lower in the group of 400 mg (9,8% in Group A vs 19,7% in the Group B, p = 0.011). Given that there was an imbalance between groups in the body weight (66.9 +/- 14 vs. 61.9 +/- 13.165 kg, p < 0.001) and BMI (24.63 +/- 4.861 vs. 22.54 +/- 3.092, p < 0.001), we decided to perform a binary logistic regression setting patient’s weight and BMI as confounding variables. The result confirms a higher risk of suboptimal progesterone levels (<8.8) with the 2x200 mg regimen (OR: 2.52 95%CI: 1.28–4.96; p = 0.007). Mean progesterone levels were similar in both groups (13,8035 ng/mL +/- 4.62159 vs. 13.9799 ng/mL +/- 7.73243 respectively, p = 0.146). No differences were observed in clinical outcomes: PR (52.3% vs. 53.1%, p = 0.881), BM (14.7% vs. 17.6%, p = 0.597), CM (20% vs. 18.6%, p = 0.819) and OPR (33.1% vs. 33.7%, p = 0.912). The subjective medical decision to administer additional progesterone from the day of the embryo transfer onwards (taking values other than 8.8 ng / mL as a reference), was significantly lower in the group of 400 mg (24,3% vs 37,3%, p = 0.009 ). Limitations, reasons for caution The inherent limitations of a retrospective analysis. The study was not powered to detect differences in clinical outcomes. Therefore, results other than progesterone levels should be interpreted with caution. Wider implications of the findings: A single pessary of 400 mg minimizes the necessity of additional medication (usually subcutaneous progesterone). Presentation of 400 mg is superior to 2x200 providing adequate progesterone levels and patient comfort. Dose finding and pharmacokinetics studies of the vaginal administration will be necessary for the future to optimize FET under AC. Trial registration number NCT04722471

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

scholarly journals P–595 Systematic dydrogesterone supplementation of artificial endometrial preparation cycles for frozen-thawed embryo transfer during Covid–19 pandemic: a good way to limit monitoring visits and optimize outcomes

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Cedri. . Durnerin ◽  
M Peigné ◽  
J Labrosse ◽  
M Guerout ◽  
C Vinolas ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Live Birth ◽  
Endometrial Thickness ◽  
Pregnancy Rates ◽  
Ongoing Pregnancy ◽  
Live Birth Rates ◽  
Endometrial Preparation ◽  
Time Periods ◽  
Frozen Thawed Embryo Transfer ◽  
Thawed Embryo Transfer

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 &lt; 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 &gt;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 &lt;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 &lt;11 ng/ml at D1 while 72 were performed in phase following introduction of vaginal P without dydrogesterone supplementation in patients with P &gt; 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

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&gt;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

Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone

2020 ◽  
Author(s):  
Elena Labarta ◽  
Giulia Mariani ◽  
Stefania Paolelli ◽  
Cristina Rodriguez-Varela ◽  
Carmina Vidal ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cohort Study ◽  
Embryo Transfer ◽  
Prospective Cohort ◽  
Independent Factor ◽  
Ongoing Pregnancy ◽  
Multivariate Logistic Regression ◽  
Serum Progesterone ◽  
Endometrial Preparation ◽  
Day Of Embryo Transfer

Abstract STUDY QUESTION Is there a serum progesterone (P) threshold on the day of embryo transfer (ET) in artificial endometrium preparation cycles below which the chances of ongoing pregnancy are reduced? SUMMARY ANSWER Serum P levels &lt;8.8 ng/ml on the day of ET lower ongoing pregnancy rate (OPR) in both own or donated oocyte cycles. WHAT IS KNOWN ALREADY We previously found that serum P levels &lt;9.2 ng/ml on the day of ET significantly decrease OPR in a sample of 211 oocyte donation recipients. Here, we assessed whether these results are applicable to all infertile patients under an artificial endometrial preparation cycle, regardless of the oocyte origin. STUDY DESIGN, SIZE, DURATION This prospective cohort study was performed between September 2017 and November 2018 and enrolled 1205 patients scheduled for ET after an artificial endometrial preparation cycle with estradiol valerate and micronized vaginal P (MVP, 400 mg twice daily). PARTICIPANTS/MATERIALS, SETTING, METHODS Patients ≤50 years old with a triple-layer endometrium ≥6.5 mm underwent transfer of one or two blastocysts. A total of 1150 patients treated with own oocytes without preimplantation genetic testing for aneuploidies (PGT-A) (n = 184), own oocytes with PGT-A (n = 308) or donated oocytes (n = 658) were analyzed. The primary endpoint was the OPR beyond pregnancy week 12 based on serum P levels measured immediately before ET. MAIN RESULTS AND THE ROLE OF CHANCE Women with serum P levels &lt;8.8 ng/ml (30th percentile) had a significantly lower OPR (36.6% vs 54.4%) and live birth rate (35.5% vs 52.0%) than the rest of the patients. Multivariate logistic regression showed that serum P &lt; 8.8 ng/ml was an independent factor influencing OPR in the overall population and in the three treatment groups. A significant negative correlation was observed between serum P levels and BMI, weight and time between the last P dose and blood tests and a positive correlation was found with age, height and number of days on HRT. Multivariate logistic regression showed that only body weight was an independent factor for presenting serum P levels &lt;8.8 ng/ml. Obstetrical and perinatal outcomes did not differ in patients with ongoing pregnancy regardless of serum P levels being above/below 8.8 ng/ml. LIMITATIONS, REASONS FOR CAUTION Only women with MVP were included. Extrapolation to other P administration forms needs to be validated. WIDER IMPLICATIONS OF THE FINDINGS This study identified the threshold of serum P as 8.8 ng/ml on the day of ET for artificial endometrial preparation cycles necessary to optimize outcomes, in cycles with own or donated oocytes. One-third of patients receiving MVP show inadequate levels of serum P that, in turn, impact the success of the ART cycle. Monitoring P levels in the mid-luteal phase is recommended when using MVP to adjust the doses according to the needs of the patient. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER NCT03272412.

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