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

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

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P–335 Endometrial compaction 5–10% is associated with the best live birth rate in artificial frozen-thawed embryo transfer cycles

Human Reproduction ◽

10.1093/humrep/deab130.334 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

E Yaprak ◽

Y E Sukur ◽

B Ozmen ◽

M Sonmezer ◽

B Berker ◽

...

Keyword(s):

Pregnancy Outcome ◽

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Endometrial Thickness ◽

Live Birth Rate ◽

Follicular Phase ◽

Endometrial Preparation ◽

Frozen Thawed Embryo Transfer ◽

Thawed Embryo Transfer

Abstract Study question What is the effect of endometrial compaction on live birth rate in frozen-thawed embryo transfer (FET) cycles? Summary answer In FET cycles with artificial endometrial preparation, the chance for live birth was significantly higher in cycles with endometrial compaction. What is known already Most studies conclude that thinner the endometrium poorer the pregnancy outcome. These studies mostly include measurements in the follicular phase. Since endometrial thickness indicates receptivity, one may expect the endometrial thickness measured on ET day to be more important to predict the outcome. However, few studies assessed endometrial thickness on ET day and unlike follicular phase studies conflicting results were obtained regarding pregnancy outcome. The change in endometrial thickness may be more valuable to predict the pregnancy outcome rather than a single measurement. Study design, size, duration Retrospective observational cohort study. 283 FET cycles in which all patients underwent artificial endometrial preparation were reviewed. Participants/materials, setting, methods: The inclusion criteria were artificial endometrial preparation, age between 20–38 years. The same protocol was applied to all patients for the endometrial preparation.The change of endometrial thickness between the end of estrogen phase and embryo transfer day was recorded. Any decrement is defined as endometrial compaction. The patients were grouped according to the changes of endometrial thicknesses as compaction and non-compaction. Main results and the role of chance Among 283 cycles, 89 had endometrial compaction and 194 did not have compaction. The clinical pregnancy, implantation and live birth rates were significantly higher in the compaction group when compared to non-compaction group (P values 0.007, 0.009, and 0.039, respectively). In order to evaluate the results according to the degree of compaction, we divided the patients into 5% compaction slices. The live birth rate was significantly higher in the 5–10% compaction group (P = 0.016). A multivariable logistic regression analysis was performed to examine the independent effects of different variables on live birth chance.In FET cycles with artificial endometrial preparation, the chance for live birth was significantly higher in cycles with endometrial compaction (OR: 2.352, 95% confidence interval {CI} 1.297–4.264, P = 0.005). A receiver operating characteristic (ROC) curve analysis was performed to evaluate whether there was a certain threshold of endometrial thickness at the end of estrogen phase for endometrial compaction to occur. The sensitivity and specificity of 9.25 mm at the end of estrogen phase calculated from the ROC curve were 76.4% and 58.8%, respectively (area under the curve: 0.701, 95% CI 0.640–0.763; P < 0.001). Limitations, reasons for caution The main limitations of the study were its retrospective nature, relatively small sample size and utilization of different ultrasound techniques at different measurements (using transvaginal ultrasound at the end of the estrogen phase and transabdominal ultrasound on ET day). Wider implications of the findings: Recently a cohort study they found that endometrial compaction results in better pregnancy outcomes, similar to our findings. But, this is the first study to suggest a threshold value (9.2) for endometrial thickness before the commencement of progesterone in regards to increase the chance of compaction. Trial registration number Not applicable

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P–696 The duration of estrogen treatment prior to frozen-blastocyst transfer does not impact live birth rate

Human Reproduction ◽

10.1093/humrep/deab130.695 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

A Reignier ◽

J Joly ◽

M Rosselot ◽

T Goronflot ◽

P Barrière ◽

...

Keyword(s):

Multivariate Analysis ◽

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Live Birth Rate ◽

Frozen Embryo Transfer ◽

Estrogen Treatment ◽

Blastocyst Transfer ◽

Oestrogen Treatment ◽

Significant Difference

Abstract Study question Does the prolonged duration of oestrogen treatment prior to frozen-blastocyst transfer (FET) affect live birth rate? Summary answer Variation in the duration of estrogen treatment prior to frozen-blastocyst transfer does not impact live birth rate. What is known already With improvements in cryopreservation techniques and fertility preservation, single embryo transfer policy and the increase in freeze-all cycles, frozen blastocyst transfer (FET) has strongly risen over the last years. Artificial endometrial preparation (AEP) is often used prior to FET. The endometrium is prepared by a sequentially treatment of estrogen and progesterone in order to synchronize endometrium and the embryo development. Whether the duration of progesterone administration before FET is well established, the optimal estrogen treatment duration remains controversial. Study design, size, duration All consecutive frozen thawed autologous blastocyst transfer cycles conducted between January 1, 2012 and July 1, 2019 in our University IVF center were included in this retrospective cohort study. We included 2235 single blastocyst FET cycles prepared with hormonal replacement therapy using oral E2 and vaginal progesterone administration in 1376 patients aged from 18 to 43 years. Participants/materials, setting, methods Patient’s characteristics, stimulation characteristics, FET cycles characteristics and cycles outcomes were anonymously recorded and analyzed. Univariate and multivariate analysis were performed. At first, each FET cycle was analyzed individually and secondly taking into account that some of the patients had undergone several FET, the model considered the number of implanting attempts for each woman. Main results and the role of chance We found no significant difference in the mean duration of estradiol administration before frozen embryo transfer between the group live birth versus non-live birth (27.0 ± 5.4 days versus 26.6 ± 5.0 days ; p=0.11). Endometrial thickness was not significantly different between the 2 groups (8.3 ± 1.7 mm versus 8,2 ± 1,7 mm ; p = 0.21). When the duration of estradiol exposure was analyzed in weeks, we observed no difference for the £ 21 days group (OR = 0.97 ; IC 0.64–1.47 ; p = 0.88), 29–35 days group (OR = 0.89 ; IC 0.68–1.16 ; p = 0.37) and > 35 days group (OR = 0.75 ; IC 0.50–1.15 ; p = 0.10) compared to the reference group (22–28 days). After multivariate analysis, the duration of estradiol treatment before frozen embryo transfer did not affect live birth. Limitations, reasons for caution The relatively limited numbers of cycles with more than 35 days or less than 21 days as well as the retrospective design of the study are significant limitations. Wider implications of the findings: Variation in the duration of estradiol supplementation before progesterone initiation does not impact FET outcomes. We therefore can be reassuring with our patients when E2 treatments need to be extended, allowing flexibility in scheduling the day of transfer. Trial registration number Not applicable

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Not throwing away my shot but taking less: three-arm randomized controlled trial finds equivalent live birth rate with intramuscular progesterone every third day for programmed frozen embryo transfer cycles

Fertility and Sterility ◽

10.1016/j.fertnstert.2021.06.060 ◽

2021 ◽

Author(s):

Leah Hawkins Bressler ◽

Jennifer E. Mersereau

Keyword(s):

Randomized Controlled Trial ◽

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Controlled Trial ◽

Live Birth Rate ◽

Frozen Embryo Transfer ◽

Randomized Controlled

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Impact of Endometrial Thickness and Volume Compaction on the Live Birth Rate Following Fresh Embryo Transfer of In Vitro Fertilization

Journal of Ultrasound in Medicine ◽

10.1002/jum.15830 ◽

2021 ◽

Author(s):

Mei T. Lam ◽

Hang W. R. Li ◽

Ernest H. Y. Ng

Keyword(s):

In Vitro Fertilization ◽

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Endometrial Thickness ◽

Live Birth Rate ◽

Fresh Embryo Transfer ◽

Vitro Fertilization

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P–304 The endometrial preparation protocol does not affect the live-birth-rate after vitrified-warmed euploid single blastocyst transfers: an analysis of 1884 procedures

Human Reproduction ◽

10.1093/humrep/deab130.303 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

C Petriglia ◽

A Vaiarelli ◽

D Cimadomo ◽

C Gentile ◽

F Fiorini ◽

...

Keyword(s):

Live Birth ◽

Gestational Age ◽

Birth Rate ◽

Live Birth Rate ◽

Blastocyst Transfer ◽

Workload Management ◽

Endometrial Preparation ◽

Blastocyst Quality ◽

The Impact ◽

Micronized Progesterone

Abstract Study question Is the live-birth-rate (LBR) different when comparing artificial (AC) and modified-natural (M-NC) cycle for endometrial preparation to vitrified-warmed euploid blastocyst transfer? Summary answer The LBR after vitrified-warmed euploid blastocyst transfer seem independent of the endometrial preparation administered. What is known already Only the transfer of a competent embryo on a receptive endometrium might result in successful implantation. Three main protocols for endometrial preparation to vitrified-warmed embryo transfer exist: NC, M-NC, and AC. None among them, though, has been shown more appropriate than the others to date, especially since, only in a few studies, the analysis was restricted to single euploid blastocyst transfers to limit the impact of embryonic issues on implantation. In conclusion, no clear consensus exists and the choice is still largely based on menstrual/ovarian cycle characteristics and patient’s needs. Study design, size, duration All first vitrified-warmed single euploid blastocyst transfers performed between April–2013 and March–2020 were included in the analysis. Endometrial preparation was conducted with either an AC (N = 1211) or a M-NC (N = 673). The protocol was chosen based on patients’ logistical reasons. The primary outcome was the LBR per transfer. Sub-analyses based on blastocyst quality and day of development were conducted. Birthweight, gestational age, gestational and perinatal issues were secondary outcomes. Participants/materials, setting, methods AC: oral estradiol-valerate 3-times/day from day2–3 of the cycle until the endometrial thickness reached ≥7mm, then 600 mg/day of micronized progesterone. The transfer was conducted on day6 of progesterone administration. M-NC: an intramuscular dose of 10,000IU hCG was administrated when the leading follicle was >17 mm and the endometrium was thicker than 7mm and trilaminar, plus 400 mg/day of micronized-progesterone as luteal phase support starting 36–40hr post-hCG. The transfer was conducted on day7 after trigger. Main results and the role of chance The two groups were similar for maternal age at retrieval (38.0±3.3yr) and transfer (38.3±3.3yr), reproductive history, embryological outcomes of the IVF cycle, body-mass-index, basal hormonal levels, and blastocyst features (Gardner’s classification: AA = 73%, AB/BA=11%, BB/AC/CA=8%, CC/BC/CB=8%; day5=48%, day6=47%, day7=5%). The LBR was 46.7% (N = 565/1211) and 49.9% (N = 336/673) after AC and M-NC, respectively, resulting in an odds-ratio 1.14, 95%CI:0.94–1.37. The absence of significant differences was confirmed also when adjusted for blastocyst quality and day of full-development (1.16, 95%CI:0.96–1.41). Among the 565 and 336 deliveries, the birthweight was similar (3290.3±470.7 versus 3251.7±521.5 g, Mann-Whitney-U-test=0.5), the gestational age was similar (38.5±1.7 versus 38.4±1.9 weeks, Mann-Whitney-U-test=0.5). Also, the rates of newborns who were normal (81% versus 82%), large (8% versus 9%), and small (11% versus 9%) for gestational age were similar (Chi-squared-test=0.5). The rates of patients experiencing gestational (6% versus 7%) and/or perinatal issues (3% versus 3%) were also similar (Fisher’s-exact-tests=0.4). Limitations, reasons for caution This is a retrospective study conducted in poor prognosis patients indicated to preimplantation genetic testing for aneuploidies. Future randomized controlled trials and cost-effectiveness analysis are desirable, as well as studies in different patient populations. Lastly, each gestational/perinatal issue shall be analyzed per se (e.g. different placentation disorders). Wider implications of the findings: The absence of clinical and perinatal differences between the two protocols for endometrial preparation supports the adoption, whenever needed, of AC. This approach, in fact, allows a higher flexibility in patients’ and daily workload management. Trial registration number None

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Influence of surgical evacuation on pregnancy outcomes of subsequent embryo transfer cycle following miscarriage in an initial IVF cycle: a retrospective cohort study

BMC Pregnancy and Childbirth ◽

10.1186/s12884-019-2543-9 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Junan Meng ◽

Mengchen Zhu ◽

Wenjuan Shen ◽

Xiaomin Huang ◽

Haixiang Sun ◽

...

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Pregnancy Outcomes ◽

Birth Rate ◽

Endometrial Thickness ◽

Live Birth Rate ◽

First Trimester ◽

Miscarriage Rate ◽

Significant Difference ◽

Surgical Evacuation

Abstract Background It is still uncertain whether surgical evacuation adversely affects subsequent embryo transfer. The present study aims to assess the influence of surgical evacuation on the pregnancy outcomes of subsequent embryo transfer cycle following first trimester miscarriage in an initial in vitro fertilization and embryo transfer (IVF-ET) cycle. Methods A total of 645 patients who underwent their first trimester miscarriage in an initial IVF cycle between January 2013 and May 2016 in Nanjing Drum Tower Hospital were enrolled. Surgical evacuation was performed when the products of conception were retained more than 8 h after medical evacuation. Characteristics and pregnancy outcomes were compared between surgical evacuation patients and no surgical evacuation patients. The pregnancy outcomes following surgical evacuation were further compared between patients with ≥ 8 mm or < 8 mm endometrial thickness (EMT), and with the different EMT changes. Results The EMT in the subsequent embryo transfer cycle of surgical evacuation group was much thinner when compared with that in the no surgical evacuation group (9.0 ± 1.6 mm vs. 9.4 ± 1.9 mm, P = 0.01). There was no significant difference in implantation rate, clinical pregnancy rate, live birth rate or miscarriage rate between surgical evacuation group and no surgical evacuation group (P > 0.05). The live birth rate was higher in EMT ≥ 8 mm group when compared to < 8 mm group in surgical evacuation patients (43.0% vs. 17.4%, P < 0.05). Conclusions There was no significant difference in the pregnancy outcomes of subsequent embryo transfer cycle between surgical evacuation patients and no surgical evacuation patients. Surgical evacuation led to the decrease of EMT, especially when the EMT < 8 mm was association with a lower live birth rate.

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