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.

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

scholarly journals Association between serum progesterone levels on the day of frozen-thawed embryo transfer and pregnancy outcomes after artificial endometrial preparation

2020 ◽  
Author(s):  
Jing Zhu ◽  
Qianqian Zhu ◽  
Jialyu Huang ◽  
Meiting Qiu ◽  
Yanwen Zhu ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Luteal Phase ◽  
Serum Progesterone ◽  
Endometrial Preparation ◽  
Vaginal Progesterone ◽  
Frozen Thawed Embryo Transfer ◽  
Thawed Embryo Transfer

Abstract Background Previous studies have examined that a range of optimal serum P level during the implantation period was associated with optimal live birth rates. However, those results obtained with vaginal or intramuscular route of progesterone administration for LPS alone. Is there a relationship between the serum progesterone (P) on the day of frozen-thawed embryo transfer (FET) with the likelihood of a live birth(LB) in artificial cycles(AC) when using a combination of oral dydrogesterone and vaginal progesterone for luteal phase support (LPS)? Methods This was a retrospective study of 3659 FET cycles with artificial endometrial preparation in a Chinese tertiary-care academic medical centre from January 2015 to February 2017. Endometrial preparation was performed using estradiol (E 2 ) valerate (Fematon-red tablets) 8 mg/d beginning on day 3 of the cycle, followed by administration of P both orally (40 mg dydrogesterone and 8 mg E 2 twice per day, Fematon-yellow tablets) and vaginally (400 mg/d; Utrogestan). The primary endpoint was LBR. The association between the serum P level on the embryo transfer day and pregnancy outcomes was evaluated by univariable and multivariable logistic regression analysis. Results Mean serum P on the day of embryo transfer was 10.30 ± 3.88 ng/ml (percentiles: 25, 7.9; 50, 9.7; 75, 12.1). The LBRs according to the serum P quartiles were as follows: Q1, 35.7%; Q2, 37.4%; Q3, 39.1%; and Q4: 38.9%. Logistic regression analysis showed that the odds of a LB were not significantly different between the low (P <7.9 ng/mL) and high (P ≥7.9 ng/mL) progesterone groups before or after adjustment (crude odds ratio [OR] = 0.89, 95% confidence interval [CI]: 0.76-1.04; adjusted OR = 0.89, 95% CI: 0.75-1.04). Conclusions The present study suggests that the serum P levels on the day of ET do not correlate with the likelihood of a LB in artificial cycles when using a combination of oral dydrogesterone and vaginal progesterone for luteal phase support. In addition, prospective, randomized, controlled, blinded trials are merited to determine the optimal dosing regimen for oral dydrogesterone in in AC-FET for LPS.

Preparation of endometrium for frozen embryo transfer cycles

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (2) ◽  
pp. 17-21
Author(s):  
Yana A. Petrosyan ◽  
Anastasiya G. Syrkasheva ◽  
Andrey Yu. Romanov ◽  
Nataliya P. Makarova ◽  
Elena A. Kalinina
Keyword(s):  
Menstrual Cycle ◽  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Frozen Embryo Transfer ◽  
Natural Cycle ◽  
Estrogen Dose ◽  
Group 2 ◽  
Frozen Thawed Embryo Transfer ◽  
Thawed Embryo Transfer ◽  
Group 1

Aim. Aim of the study was to the effectiveness of various endometrial preparation protocols in IVF frozen embryo transfer cycles. Materials and methods. The study included 288 women, which were stratified into two groups depending on the onset of pregnancy: group 1 pregnancy + (n=92), group 2 pregnancy - (n=196). Then endometrium preparation features were evaluated. Results. The pregnancy rate after frozen-thawed embryo transfer was a bit higher in the natural menstrual cycle (41.2%) compared to the hormonal replacement therapy (30.0%); p=0.083. There were no significant differences in the use of various estrogen and progestogen drugs, the average estrogen dose, progestogen administration and the endometrium thickness. In the natural cycle, the odds ratio of pregnancy with the duration menstrual cycle from 28 to 30 days was 4.25 (95% CI 1.15; 17.23). Conclusion. Thus, the pregnancy rate is slightly higher in natural cycle frozen-thawed embryo transfer. However, the duration of the menstrual cycle (from 28 to 30 days) has a key effect on the effectiveness of the IVF program in this case.

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 (&lt;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

scholarly journals Uterus Size May Affect Reproductive Outcome in Women with Adenomyosis After Gnrh- Agonist Pretreatment Undergoing Frozen Embryo Transfer Cycles: A Retrospective Cohort Study

2020 ◽  
Author(s):  
Wei Xiong ◽  
Ruiyi Tang ◽  
Peng Wu ◽  
Zhengyi Sun ◽  
jingran zhen ◽  
...  
Keyword(s):  
Cohort Study ◽  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Live Birth ◽  
Gnrh Agonist ◽  
Retrospective Cohort Study ◽  
Pregnancy Outcomes ◽  
Retrospective Cohort ◽  
Clinical Pregnancy ◽  
Frozen Embryo Transfer

Abstract Background: GnRH-agonist is used to treat adenomyosis, but its efficacy in adenomyosis patients with uterine enlargement undergoing frozen embryo transfer (FET) is unclear. Methods：The retrospective cohort study comprised 112 adenomyosis patients with uterine enlargement undergoing the first FET circle. A long-term GnRH-a pretreatment was administered to 112 patients with uterine enlargement. These patients were divided into two groups according to the therapeutic effect: patients with a normal-size uterus after GnRH-a treatment (GN group) and patients with an enlarged uterus after GnRH-a treatment (GL group). Results：Not all patients can shrink their uterus to a satisfactory level. After receiving GnRH-a pretreatment, the uterus returned to normal size in 77% of patients (GN group), and 23% of patients had a persistently enlarged uterus (GL group). The pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were significantly higher in the GN group than in the GL group. Controlling for the confounding factors, normal uterus size (odds ratio [OR] 4.50; P=0.03) and low body mass index (OR 3.13; P=0.03) affected the odds of achieving live birth. The cut-off value selected on the ROC curve of uterus volume after GnRH-a treatment for detecting live birth was 144.7Conclusions：GnRH-a pretreatment was associated with the regression of adenomyosis lesions and improved clinical pregnancy outcomes in the adenomyosis patients with uterine enlargement whose lesion are GnRH-a susceptible on FET cycles. However, about a quarter of patients may not be less responsive to GnRH-a and have poorer pregnancy outcomes, especially in overweight women.

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