Low progesterone levels on the day before natural cycle frozen embryo transfer are negatively associated with live birth rates

2020 ◽  
Vol 35 (7) ◽  
pp. 1623-1629
Author(s):  
Sofia Gaggiotti-Marre ◽  
Manuel Álvarez ◽  
Iñaki González-Foruria ◽  
Mònica Parriego ◽  
Sandra Garcia ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Embryo Transfer ◽  
Live Birth ◽  
Luteal Phase ◽  
Frozen Embryo Transfer ◽  
Natural Cycle ◽  
Reproductive Outcomes ◽  
Endometrial Preparation ◽  
Urine Testing ◽  
The Impact

Abstract STUDY QUESTION Are progesterone (P) levels on the day before natural cycle frozen embryo transfer (NC-FET) associated with live birth rate (LBR)? SUMMARY ANSWER Regular ovulatory women undergoing NC-FET with serum P levels <10 ng/ml on the day before blastocyst transfer have a significantly lower LBR than those with serum P levels >10 ng/ml. WHAT IS KNOWN ALREADY The importance of serum P levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established. However, no study has analyzed the importance of serum P levels in patients undergoing FET under a true natural endometrial preparation cycle. STUDY DESIGN, SIZE, DURATION This was a retrospective cohort study including 294 frozen blastocyst transfers under natural cycle endometrial preparation at a university-affiliated fertility centre between January 2016 and January 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients had regular menstrual cycles and underwent NC-FET with their own oocytes. Only patients who had undergone serum P measurement between 8 am and 11 am on the day before FET were included. Patients did not receive any external medication for endometrial preparation or luteal phase support. Patients were divided into two groups according to serum P levels below or above 10 ng/ml on the day before FET. Univariate analysis was carried out to describe and compare the cycle characteristics with reproductive outcomes. To evaluate the effect of P, a multivariable logistic model was fitted for each outcome after adjusting for confounding variables. MAIN RESULTS AND THE ROLE OF CHANCE Mean serum P levels on the day before FET were significantly higher in patients who had a live birth compared to those who did not (14.5 ± 7.0 vs 12.0 ± 6.6 ng/ml, 95% CI [0.83; 4.12]). The overall clinical pregnancy rate (CPR) and LBR were 42.9% and 35.4%, respectively. Patients in the higher P group (>10 ng/ml) had a higher LBR (41.1% vs 25.7%: risk difference (RD) 15.4%, 95% CI [5; 26]) and CPR (48.6% vs 33.0%: RD 15.6%, 95% CI [4; 27]). Patients with higher serum P levels on the day before FET (63% of patients) had an improved LBR (odds ratio: 1.05; 95% CI [1.02; 1.09]). Women with serum P levels <10 ng/ml on the day before FET (37% of patients) had significantly higher weights (62.5 ± 9.9 vs 58.1 ± 7.1 kg, 95% CI [1.92; 6.90]) and BMI (22.9 ± 3.6 vs 21.6 ± 2.7 kg/m2, 95% CI [0.42; 2.25]) compared to patients with P levels >10 ng/ml. LIMITATIONS, REASONS FOR CAUTION The main limitation of our study is its retrospective design. Other potential limitations are the detection of LH surge through urine testing and the inclusion of patients who did and did not undergo preimplantation genetic testing for aneuploidies. The protocol used in our institution for monitoring NC-FET does not look for the onset of progesterone secretion by the corpus luteum, and a slow luteinisation process or delay of corpus luteum function cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS We provide evidence that a minimum serum P threshold (P >10 ng/ml) might be required for improved reproductive outcomes in NC-FET. This result suggests that there are different mechanisms by which P is produced and/or distributed by each patient. This study also provides an excellent model to evaluate the impact of luteal phase defect through NC-FET. A prospective evaluation to assess whether P supplementation should be individualised according to patient’s needs is necessary to support our findings. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used, and there are no competing interests.

P–677 Endometrial thickness, endometrial preparation protocol and number of euploid embryos transferred, significantly impact the live birth in frozen embryo transfer cycles

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Liñá. Tegedor ◽  
I Elkhatib ◽  
A Abdala ◽  
A Bayram ◽  
K Ab. Ali ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Embryo Transfer ◽  
Live Birth ◽  
Birth Rate ◽  
Endometrial Thickness ◽  
Live Birth Rate ◽  
Frozen Embryo Transfer ◽  
Endometrial Preparation ◽  
The Impact ◽  
Ploidy Status

Abstract Study question Is the live birth rate (LBR) in euploid frozen embryo transfer (FET) cycles affected by the endometrial thickness (EMT)? Summary answer A significantly higher LBR was observed in patients with an endometrial thickness of at least 7.5mm (46.24% vs. 54.63%) What is known already Parameters assessing the endometrium prior planning a FET include endometrial thickness, pattern and blood flow. The impact of the endometrial thickness on ART outcomes is controversial, with conflicting results published. A recent meta-analysis evaluated whether EMT could predict pregnancy outcomes and suggested that lower EMT was associated with lower incidence of clinical pregnancy rate (CPR), implantation rate (IR) and LBR. Due to heterogeneity of parameters evaluated between different publications, where embryos with unknown ploidy status were transferred, in conjunction with variability of stimulation protocols and the number of embryos transferred, the real effect of the EMT was difficult to infer. Study design, size, duration This was a two-center retrospective observational study including a total of 1522 euploid FET cycles between March 2017 and March 2020 at ART Fertility Clinics Muscat, Oman and Abu Dhabi, UAE. Participants/materials, setting, methods Trophectoderm biopsies were analyzed with Next Generation Sequencing (NGS). Vitrification/warming of blastocysts was performed using Cryotop method (Kitazato). EMT was measured by vaginal ultrasound prior initiating the progesterone administration (± 1 day) and LBR was recorded. Multivariate analysis was performed between LB outcomes and median EMT while controlling for confounding factors. Main results and the role of chance A total of 1522 FET cycles were analyzed: 975 single embryo transfer (SET) and 547 double embryo transfer (DET). The mean age of the patients was 33.38 years with a mean BMI of 27.1 kg/m2. FET were performed in EMT ranging from 3 to 15 mm and 50.52% resulted in a live birth. Though potentially all ranges of EMT were associated with LB, the median EMT in patients with LB was significantly higher than the median EMT of patients without LB (7.6mm vs. 7.4mm; p < 0.001). The dataset was stratified into two groups based on the median EMT (7.5mm): < 7.5mm (n = 744 cycles) and ≥ 7.5mm (n = 778 cycles). A significantly higher live birth rate was observed in ≥ 7.5mm group (46.24% vs. 54.63%. p = 0.0012). In multivariate analysis, EMT, FET endometrial preparation protocol, and number of embryos transferred were the main parameters influencing the chance to achieve LB: OR 1.10 [1.01–1.19], p < 0.015 for the EMT; OR 1.84 [1.47–2.30], p < 0.0001 for Natural Cycle protocol and OR 1.55 [1.25–1.93], p < 0.0001 for DET. Intercept 0.18 [0.07–0.44] p < 0.0002. Female age did not reach significance: OR 1.02 [1.00–1.04], p = 0.056. Limitations, reasons for caution Besides the retrospective nature of the study, the inter-observer variability in EMT assessment between different physicians is a limitation. The physician and embryologist performing the embryo transfer could not been standardized due to the multicenter design of the study. Wider implications of the findings: The EMT in FET may influence the LBR and should be considered as an important factor for the success of embryo transfer cycles. Whether these results can be extrapolated to fresh embryo transfer and to blastocysts with unknown ploidy status, needs further investigation. Trial registration number Not applicable

scholarly journals Natural vs. programmed cycles for frozen embryo transfer: study protocol for an investigator-initiated, randomized, controlled, multicenter clinical trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sheriza Baksh ◽  
Anne Casper ◽  
Mindy S. Christianson ◽  
Kate Devine ◽  
Kevin J. Doody ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Embryo Transfer ◽  
Live Birth ◽  
Frozen Embryo Transfer ◽  
Obstetric Outcomes ◽  
Natural Cycle ◽  
Fresh Embryo Transfer ◽  
Maternal Risk ◽  
Link Type ◽  
Parallel Group

Abstract Background Randomized trials of assisted reproductive technology (ART) have been designed for outcomes of clinical pregnancy or live birth and have not been powered for obstetric outcomes such as preeclampsia, critical for maternal and fetal health. ART increasingly involves frozen embryo transfer (FET). Although there are advantages of FET, multiple studies have shown that risk of preeclampsia is increased with FET compared with fresh embryo transfer, and the reason for this difference is not clear. NatPro will compare the proportion of preeclampsia between two commonly used protocols for FET,modified natural and programmed cycle. Methods In this two-arm, parallel-group, multi-center randomized trial, NatPro will randomize 788 women to either modified natural or programmed FET and follow them for up to three FET cycles. Primary outcome will be the proportion of preeclampsia in women with a viable pregnancy assigned to a modified natural cycle FET (corpus luteum present) protocol compared to the proportion of preeclampsia in pregnant women assigned to a programmed FET (corpus luteum absent) protocol. Secondary outcomes will compare the proportion of live births and the proportion of preeclampsia with severe features between the protocols. Conclusion This study has a potential significant impact on millions of women who pursue ART to build their families. NatPro is designed to provide clinically relevant guidance to inform patients and clinicians regarding maternal risk with programmed and modified natural cycle FET protocols. This study will also provide accurate point estimates regarding the likelihood of live birth with programmed and modified natural cycle FET. Trial registration ClinicalTrials.govNCT04551807. Registered on September 16, 2020

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–237 The good, the fast and the slow: which is better? Live birth rate following single blastocyst frozen embryo transfer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P Sokol ◽  
E Clu. Obradó ◽  
M Sol Inarejos ◽  
M Parrieg. Beltrán ◽  
F Martíne. Sa. Andrés ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Embryo Transfer ◽  
Live Birth ◽  
Embryo Quality ◽  
Frozen Embryo Transfer ◽  
Birth Rates ◽  
Live Birth Rates ◽  
Actual Effect ◽  
Blastocyst Quality ◽  
The Impact

Abstract Study question Are embryo quality and day of vitrification (Day 5, 6 or 7) associated with live birth rates (LBR) following single blastocyst transfer (SBT) in frozen embryo transfer cycle (FET)? Summary answer Both blastocyst quality and day of vitrification are significantly associated with LBRs, with very low LBR when poor quality embryos are frozen on day 6. What is known already Evidence suggests that chromosomal status (ploidy) is strongly associated with blastocyst morphology and good quality embryos are more likely to be euploid. Furthermore, previous studies have shown a relationship between the time that embryos need to reach blastocyst stage and their euploidy rate with slowly developing blastocysts showing higher rate of aneuploidy. Nonetheless, despite all this evidence little is known about the actual effect of the combination of blastocyst quality and day of its vitrification. The scope of this study was to quantify the actual effect of the embryo quality and day of vitrification on live birth rates following FET. Study design, size, duration Retrospective analysis of 1546 FET cycles with SBT conducted between 2017 and 2019 in the university-affiliated private clinic. The embryos used for FET were obtained from IVF/ICSI: with PGT (FET-PGT) or without PGT (FET0) or from donated oocytes (FET-DON). Participants/materials, setting, methods FET with natural, natural-modified and completely medicated cycles to prepare endometrial lining were included. Blastocysts were classified according to Spanish Association for the Study of Reproductive Biology (ASEBIR) classification, ranging from A (the highest) to D (the lowest). The impact on LBR of different subgroups, formed within FET-PGT, FET0, FET-DON groups due to different day of vitrification and blastocyst quality, was assessed, using logistic regression after adjusting for age, day of vitrification and embryo quality. Main results and the role of chance We included 1546 FET cycles. Of those, 543 (35%) corresponded to FET-PGT; 648 (42%) to FET0 and 355 (23%) to FET-DON cycles. Overall, 1051 (68%) embryos were frozen on day 5(D5), 472 (30.5%) on day 6(D6) and 23 (1.5%) on day 7(D7). As far as embryo quality was concerned, 215 (13.9%) grade A; 957 (61.9%) B; 371(24%) C and 3(0.2%) D blastocysts were transferred. LBRs were significantly different between different embryos frozen on D5 44.3%; on D6 28.8% and on D7 8.7%, p < 0.001. When blastocyst quality was considered, LBR were 48.4% for grade A; 42.5% for B; 25.1% for C and 0% for D, p < 0.001. After applying logistic regression analysis, the odds ratio (OR) for transferring D6-blastocyst was 1.08, 95% CI[0.45; 2.62] and blastocyst with grade B and C; 0.71, 95% CI[0.51; 1.00]; 0.57,95% CI[0.36; 0.88] respectively. However, after transferring D6-blastocyst graded as C, the OR was 0.33, 95% CI[0.12; 0.90]. Our predictive model showed that the impact of the embryo quality on LBR was sustained across three groups. Transfer of D5/D6 grade A blastocyst resulted in the highest, while D6-C in the lowest LBR in all the groups. In the latter case vitrification on D6 impaired additionally the outcome. Limitations, reasons for caution The study should be interpreted with caution due to its retrospective character and the assessment of blastocyst quality on the day of vitrification and not on the day its transfer. Wider implications of the findings: Our robust findings could be considered a useful tool for counselling couples who seek advice regarding their expected success rates in the setting of FET with SBT. The very low livebirth rates in low quality (C) slow developing (D6) embryos should be communicated to patients prior to planning a FET. Trial registration number Not applicable

GnRHa for trigger and luteal phase support in natural cycle frozen embryo transfer – A proof of concept study

2020 ◽  
Vol 20 (3) ◽  
pp. 282-287
Author(s):  
Itai Bar Hava ◽  
Hadar Yafee ◽  
Yeela Omer ◽  
Peter Humaidan ◽  
Hadas Ganer Herman
Keyword(s):  
Embryo Transfer ◽  
Luteal Phase ◽  
Frozen Embryo Transfer ◽  
Natural Cycle ◽  
Proof Of Concept ◽  
Luteal Phase Support ◽  
Concept Study

scholarly journals Ambient air pollution and in vitro fertilization treatment outcomes

2019 ◽  
Vol 34 (10) ◽  
pp. 2036-2043 ◽  
Author(s):  
S L Boulet ◽  
Y Zhou ◽  
J Shriber ◽  
D M Kissin ◽  
H Strosnider ◽  
...  
Keyword(s):  
Air Pollution ◽  
Treatment Outcomes ◽  
Embryo Transfer ◽  
Live Birth ◽  
Oocyte Retrieval ◽  
Ambient Air ◽  
Ambient Air Pollution ◽  
Reproductive Outcomes ◽  
Adjusted Risk ◽  
The Impact

Abstract STUDY QUESTION Is air pollution associated with IVF treatment outcomes in the USA? SUMMARY ANSWER We did not find clear evidence of a meaningful association between reproductive outcomes and average daily concentrations of particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) and ozone (O3). WHAT IS KNOWN ALREADY Maternal exposure to air pollution such as PM2.5, nitrogen oxides, carbon monoxide or O3 may increase risks for adverse perinatal outcomes. Findings from the few studies using data from IVF populations to investigate associations between specific pollutants and treatment outcomes are inconclusive. STUDY DESIGN, SIZE AND DURATION Retrospective cohort study of 253 528 non-cancelled fresh, autologous IVF cycles including 230 243 fresh, autologous IVF cycles with a transfer of ≥1 embryo was performed between 2010 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS We linked 2010–2012 National ART Surveillance System data for fresh, autologous IVF cycles with the ambient air pollution data generated using a Bayesian fusion model available through the Centers for Disease Control and Prevention’s Environmental Public Health Tracking Network. We calculated county-level average daily PM2.5 and O3 concentrations for three time periods: cycle start to oocyte retrieval (T1), oocyte retrieval to embryo transfer (T2) and embryo transfer +14 days (T3). Multivariable predicted marginal proportions from logistic and log-linear regression models were used to estimate adjusted risk ratios (aRR) and 95% CI for the association between reproductive outcomes (implantation rate, pregnancy and live birth) and interquartile increases in PM2.5 and O3. The multipollutant models were also adjusted for patients and treatment characteristics and accounted for clustering by clinic and county of residence. MAIN RESULTS AND THE ROLE OF CHANCE For all exposure periods, O3 was weakly positively associated with implantation (aRR 1.01, 95% CI 1.001–1.02 for T1; aRR 1.01, 95% CI 1.001–1.02 for T2 and aRR 1.01, 95% CI 1.001–1.02 for T3) and live birth (aRR 1.01, 95% CI 1.002–1.02 for T1; aRR 1.01, 95% CI 1.004–1.02 for T2 and aRR 1.02, 95% CI 1.004–1.03 for T3). PM2.5 was not associated with any of the reproductive outcomes assessed. LIMITATIONS, REASONS FOR CAUTION The main limitation of this study is the use of aggregated air pollution data as proxies for individual exposure. The weak positive associations found in this study might be related to confounding by factors that we were unable to assess and may not reflect clinically meaningful differences. WIDER IMPLICATIONS OF THE FINDINGS More research is needed to assess the impact of air pollution on reproductive function. STUDY FUNDING/COMPETING INTEREST(S) None.

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