Influence of endometrial thickness on pregnancy rates in modified natural cycle frozen-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 < 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

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Serum Progesterone Level at the Day Prior to Frozen Thawed Embryo Transfer and Pregnancy Rate

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2021/v33i1731047 ◽

2021 ◽

pp. 221-231

Author(s):

Merihan Mohamed Elewa ◽

Ayman Abdelaziz Eldorf ◽

Shahinaz Hamdy Elshorbagy ◽

Manal Mostafa Abdallah

Keyword(s):

Pregnancy Rate ◽

Embryo Transfer ◽

Endometrial Thickness ◽

Pregnancy Rates ◽

Observational Research ◽

Embryo Survival ◽

Serum Progesterone ◽

Laboratory Methods ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

Background: Cryopreservation's success rate varies depending on woman age, as low as 14.8% (if eggs were extracted from 40-year-old women), and as high as 31.5% with 25-year-old women. The goal of the research is to improve laboratory methods for freezing-thawing embryos, leading to elevated embryo survival rate. Yet, in hormonal replacement therapy frozen-thawed embryo transfer (HRT-FET) cycles, effective endometrial preparation before embryo transfer attracted less focus. The present research’s aim is to see whether there's a link between blood progesterone levels and pregnancy rates the day before frozen-thawed embryo transfer. Methods: This prospective observational research has investigated 120 patients of frozen-thawed embryo transfer cycle treatment, only 100 individuals subdivided to 2 groups for serum level of progesterone one day before frozen-thawed embryo transfer. The subjects visited both the Obstetrical and Gynecological Department of Tanta University as well as private centers between May 2020 and January 2021. Results: We discovered no correlation between maternal age with pregnancy test results. Yet, our study discovered highly significant variation among both groups regarding endometrial thickness one day preceding embryo transfer, and regarding pregnancy rate (p<0.05). Conclusion: The serum progesterone hormone preceding frozen embryo transfer has significant and direct relation and impact upon pregnancy rates. The present research detected low serum progesterone less than 10 nanograms/ml in the day before frozen-thawed embryo transfer in HRT-FET cycles significantly decreased probability of ongoing pregnancy post frozen-thawed embryo transfer.

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Endometrial thickness in modified natural-cycle frozen-thawed embryo transfer cycles: Should we ignore the red traffic lights?

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1111/aogs.13438 ◽

2018 ◽

Vol 98 (2) ◽

pp. 267-267

Author(s):

Marcus J. Davenport ◽

Luk J. R. Rombauts ◽

Ben W. Mol

Keyword(s):

Embryo Transfer ◽

Endometrial Thickness ◽

Natural Cycle ◽

Traffic Lights ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

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P–367 A comparison of frozen-thawed embryo transfer protocols in 3,478 frozen embryo transfers

Human Reproduction ◽

10.1093/humrep/deab130.366 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

V Bellemare ◽

E Kadou. Peero ◽

I Feferkorn ◽

W Buckett

Keyword(s):

Embryo Transfer ◽

Endometrial Thickness ◽

Oocyte Retrieval ◽

Natural Cycle ◽

Female Age ◽

Stage Embryo ◽

Embryo Stage ◽

Embryo Grade ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

Abstract Study question What frozen-thawed embryo transfer (FET) protocol is associated with the highest live birth rate (LBR)? Summary answer: Natural cycle FET (NC-FET), with or without hCG triggering are associated with higher LBR and clinical pregnancy rate (CPR) compared to artificial HRT-FET cycles. What is known already FET cycles (as opposed to fresh ET) are now the most frequently performed treatment in ART. There are many reasons for this including better laboratory cryopreservation techniques, increased single ET cycles, freeze-all cycles to reduce OHSS, as well as PGT-A and personalized ET. Nevertheless, there is no clear consensus on the most effective protocol. Study design, size, duration Retrospective cohort study with FET of cleavage (n = 220) and blastocyst (n = 3258) embryos thawed 2013–2018 in a single academic center. FET protocols were NC-FET (n = 182), artificial HRT-FET (n = 3159) and modified NC (mNC) with hCG triggering (n = 137). Other cycles (gonadotrophin or GnRH agonist) and women with uterine anomalies were excluded. Primary outcome was LBR. Secondary outcomes were CPR, visits per cycle and endometrial thickness. Adjustment was made for potential known confounders. Participants/materials, setting, methods In NC-FET, no medication was given and ET timing was by serum LH surge. In mNC-FET, hCG was given when the lead follicle reached 18mm rather than awaiting the LH surge. In artificial HRT-FET, estradiol valerate was given and once endometrial thickness reached 8mm, progesterone was added and ET was planned. Adjustment for female age at oocyte retrieval, embryo stage, embryo grade, year of freezing, year of thawing, infertility cause and endometrial thickness was performed. Main results and the role of chance There were no significant differences between the groups with regard to female age at oocyte retrieval, embryo stage, embryo grade, embryo number, cycle number and endometrial thickness. As expected, more women with irregular cycles were included in the artificial HRT-FET compared to NC-FET (16.1% vs. 8.2%, p = 0.003) and mNC-FET (16.1% vs. 4.1%, p < 0.0001). There were more visits per cycle in NC-FET and mNC-FET compared to artificial HRT_FET (p < 0.0001). LBR was higher in the mNC-FET (38.0%) and NC-FET (31.9%) compared to artificial HRT_FET (20.2%) (p = 0.0001 and p = 0.0003 respectively). CPR was higher in mNC-FET compared to artificial HRT-FET (45.3% vs. 32.3%, p = 0.0002), and in NC-FET compared to artificial HRT-FET (44.5% vs. 32.3%, p = 0.0009). There was no significant difference in LBR or CPR between NC-FET and mNC-FET. Sub-analysis of the first FET showed similar results. Biochemical pregnancy loss and miscarriage rates were similar in all groups. The higher LBR with NC-FET and mNC-FET remained significant even after adjusting for potential confounders, (aOR 2.42, 95%CI: 1.53–3.66, p < 0.0001). Limitations, reasons for caution The interpretation of the findings of this study is limited by the retrospective nature of the analysis and the potential for unmeasured confounding variables. Wider implications of the findings: Although artificial HRT FET cycles are more common, convenient and practical for clinicians, with less visits per cycle, its use must be cautiously reconsidered in light of the potential negative effect on LBR when compared with natural cycle FET. Trial registration number Not applicable

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The effect of LH rise during artificial frozen–thawed embryo transfer (FET) cycles

Reproduction and Fertility ◽

10.1530/raf-21-0017 ◽

2021 ◽

Vol 2 (3) ◽

pp. 231-235

Author(s):

Samer Khoury ◽

Einav Kadour-Peero ◽

Ilan Calderon

Keyword(s):

Luteinizing Hormone ◽

Embryo Transfer ◽

Pregnancy Outcomes ◽

Endometrial Thickness ◽

Transvaginal Ultrasound ◽

Pregnancy Rates ◽

Clinical Pregnancy ◽

The Impact ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

Purpose To evaluate the association between a rise in serum luteinizing hormone (LH) levels during artificial frozen–thawed embryo transfer (FET) cycles and clinical pregnancy rate. Methods A retrospective cohort study of women undergoing artificial FET cycles. We compared cycles in which LH double itself from the early follicular phase and further (group A) to cycles without a rise in LH (group B). Endometrium preparation was achieved by administration of 2 mg three times per day estradiol valerate tablets. Embryo transfer (ET) was conducted after achieving endometrial thickness > 7 mm and vaginal progesterone was added according to the embryo’s age. A beta-hCG was measured 13–14 days after ET. Clinical pregnancy was diagnosed on transvaginal ultrasound. Results Data from 984-FET cycles were retrieved. LH, exogenous estradiol (E2), progesterone values, endometrial thickness, and pregnancy outcomes were available in all patients. From 984-FET cycles, 629 (63.9%) had a doubling, and 355 (36.07%) had no rise in LH. Patients mean age was 30 years, similar in both groups. A multivariable logistic regression analysis was calculated to assess the effect of LH rise and pregnancy outcomes, after adjusting for confounders including a rise in E2 level and endometrial thickness. In this model, there was no association between doubling LH values and pregnancy rates (adjusted odds ratio: 1.06, 95% CI: 0.75–1.5, P = 0.74). Conclusion LH rise during artificial FET cycles does not alter pregnancy rates. Apparently, hormonal monitoring of LH levels may not yield useful information in the artificial FET cycle and may be omitted. Lay summary Supplementation of estradiol, a hormone produced by the ovaries, starting at the beginning of the menstrual cycle of an artificially frozen embryo transfer (FET) can lead to a rise in luteinizing hormone (LH), the hormone that induces ovulation. Such a rise in LH may interfere with embryo implantation, the process where the embryo attaches to the inner lining of the uterus and, therefore, could affect the chances of pregnancy. The current study is the first to assess the effect of a dynamic rise in LH levels during FET cycles on pregnancy rates. This study found no difference in pregnancy rates between FET cycles where the LH doubled compared to cycles without such a rise in LH. Larger, prospective studies should be conducted to assess the impact of LH elevation on pregnancy outcomes.

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Importance of endometrial thickness in frozen-thawed embryo transfer: difference between hormone replacement protocol and natural cycle protocol

Fertility and Sterility ◽

10.1016/j.fertnstert.2012.07.468 ◽

2012 ◽

Vol 98 (3) ◽

pp. S127

Author(s):

I.H. Park ◽

K.H. Lee ◽

H.G. Sun ◽

S.K. Kim ◽

J.H. Lee ◽

...

Keyword(s):

Embryo Transfer ◽

Endometrial Thickness ◽

Hormone Replacement ◽

Natural Cycle ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

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P–691 How predictive is endometrial thickness for live birth after fresh and frozen-thawed embryo transfer when no cut-off is employed?

Human Reproduction ◽

10.1093/humrep/deab130.690 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

E Turkgeldi ◽

B Shakerian ◽

S Yildiz ◽

I Keles ◽

B Ata

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Endometrial Thickness ◽

Treatment Success ◽

University Hospital ◽

Registration Number ◽

Fresh Frozen ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

Abstract Study question Does endometrial thickness (EMT) predict live birth (LB) after fresh and frozen-thawed embryo transfer (ET) and is there a lower EMT cut-off for ET? Summary answer Once intracavitary pathology and inadvertent progesterone exposure is excluded, EMT is not predictive for LB. EMT is not linearly associated with probability of LB. What is known already EMT is commonly used as a marker of endometrial receptivity and in turn, assisted reproductive technology treatment success. ET is often cancelled or postponed if EMT is below an arbitrary cut-off. However, the available evidence on the relationship between EMT and LB rates is conflicting and too dubious to hold such strong stance. An overwhelming majority of the studies on the subject are retrospective, they use different arbitrary cut off values ranging between 6 to 9 mm with heterogeneous stimulation and transfer protocols. Study design, size, duration Records of all women who underwent fresh or frozen-thawed ET in Koc University Hospital Assisted Reproduction Unit between October 2016 - August 2019 were retrospectively screened. All women who underwent fresh or frozen-thawed blastocyst transfer during the study period were included. Every woman contributed to the study with only one transfer cycle for each category, i.e., fresh ET and frozen-thawed ET. Participants/materials, setting, methods After ruling out endometrial pathology, EMT was measured on the day of ovulation trigger for fresh ET cycles, and on the day of progesterone commencement for frozen-thawed ET. ET was carried out, regardless of EMT, if there was no suspicion of inadvertent progesterone exposure, i.e., due to follicular phase progesterone elevation in fresh or premature ovulation in frozen ET cycles. Main results and the role of chance 560 ET cycles, 273 fresh and 287 frozen-thawed, were analyzed. EMT varied from 4mm to 18mm. EMT were similar between women who achieved a LB and who did not after fresh ET [10.5 (9.2 – 12.2) mm and 9 (8 – 11) mm, respectively, p = 0.11]. Ovarian stimulation characteristics and proportion of women who received a single embryo were similar (69% vs 68.3%, respectively, p = 0.91). Women who achieved a LB was significantly younger than those who did not [35 (32–38) and 37 (33–41), respectively, p < 0.01]. Women who had a LB and who did not after frozen-thawed ET had similar EMT of 8.4 (7.4 – 9.7) mm and 9 (8 – 10) mm, respectively (p = 0.38). Women who achieved a LB were significantly younger than those who did not [32 (29–35) vs 34 (30–38) years, p = 0.04]. The proportion of women who received a single ET was similar between women who achieved a LB and who did not after a FET [86/95 (90.5%) vs 181/192 (94.3%), respectively, p = 0.26]. Area under curve values of EMT for predicting LB in fresh, frozen-thawed and all ET were 0.56, 0.47 and 0.52, respectively. EMT and LB rate were not linearly correlated in fresh or frozen-thawed ET cycles. Limitations, reasons for caution Although our study is retrospective, no women was denied ET due to EMT in our center. Only patients undergoing ET were included in the analysis, which may introduce bias due to the selection of couples who were competent enough to produce at least one blastocyst fit for transfer. Wider implications of the findings: Since women with thin endometrium had reasonable chance for LB even in the absence of a cut-off for EMT in this unique dataset, delaying or denying ET for any given EMT value alone does not seem justified. Further studies in which ET is carried out regardless of EMT are needed. Trial registration number Not applicable

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