Subsequent Frozen-thawed Embryo Transfer Research Articles

P-425 Effect of time interval between SARS-COV-2 infection and frozen-thawed embryo transfer on pregnancy outcomes

Abstract Study question Does the time interval between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and frozen-thawed embryo transfer (FET) affect pregnancy outcomes? Summary answer Delaying the subsequent FET for at least 30 days after the SARS-COV-2 infection was associated with beneficial pregnancy outcomes. What is known already Coronavirus disease 2019 (COVID-19), as a multi-systemic disease, poses a threat to reproductive health. Despite reassuring studies have shown that SARS-CoV-2 infection does not appear to affect human oocytes and embryos in fresh cycles, there is limited data regarding the effects of SARS-CoV-2 infection on FET outcomes.Particularly, it remains unclear whether it is beneficial to postpone embryo transfer after SARS-COV-2 infection. Study design, size, duration Retrospective cohort study, including 2165 FET cycles between November 2022 and May 2023 from an academic fertility center. Participants/materials, setting, methods Participants The infected group: Patients who were infected with SARS-CoV-2 before FET. According to the different time interval from the day of infection to embryo transfer, these cycles were further categorized into four subgroups: ≤30 days, 31-60 days, 61-90 days, and ≥91 days. The non-infected group: Patients undergoing FET during the same period who were asymptomatic and tested negative. Outcome measures: rates of biochemical pregnancy (BPR), clinical pregnancy (CPR), early pregnancy loss (EPLR) and ongoing pregnancy (OPR). Main results and the role of chance A total of 997 FET cycles were included in the non-infected (32.9±3.9 years) and 1168 in the infected groups (32.7±4.1 years), among which, 82(7.0%), 212(18.2%), 471(40.3%) and 403(34.5%) were infected ≤30, 31-60, 61-90, and ≥91 days before FET, respectively. Overall, no differences were observed across the ≤30, 31-60, 61-90, ≥91 days’ subgroup and the non-infected group with respect to BPR (53.7%, 64.6%, 63.7%, 62.3%, and 66.6%, p = 0.129), CPR (46.3%, 54.7%, 56.3%, 54.6%, and 57.4%, p = 0.362), EPLR (29.5%, 24.8%, 23.3%, 22.3%, and 21.5%, p = 0.712) and OPR (37.8%, 47.2%, 48.6%, 48.1%, and 51.5%, p = 0.143). Although non-significant, a reduction in BPR, CPR and OPR was noted in those with SARS-CoV-2 infection ≤30 days before FET. Generalized estimating equations logistic regression models were applied to investigate if there’s any association between pregnancy outcomes and time interval from infection to FET while adjusting for potential confounders. Results revealed that SARS-CoV-2 infection within 30 days prior to FET was associated significantly reduced odds of biochemical pregnancy (adjusted odds ratio [aOR] 0.50, 95% confidence interval [CI] 0.31-0.80), clinical pregnancy (aOR 0.57, 95%CI 0.36-0.90) and ongoing pregnancy (aOR 0.52, 95%CI 0.32-0.84) compared to the non-infected group, while no such associations were observed with infection >30 days before FET. Limitations, reasons for caution The retrospective nature of the study and limited sample size in the ≤30 days’ subgroup limits the generalizability of the findings. Large-scale prospective studies are warranted to verify our results. Wider implications of the findings Our findings suggest that while overall, SARS-COV-2 infection has no adverse impact on pregnancy outcomes, delaying an embryo transfer for at least 30 days after an infection may be more beneficial for FET cycles. Trial registration number Not applicable.

Clinical utility of office hysteroscopy following failed invitro fertilization-embryo transfer: A retrospective cohort study.

Despite its widespread use, invitro fertilization (IVF) outcomes are challenged by implantation failure, largely due to factors such as embryo quality and endometrial receptivity. In this study, we investigated the clinical effect of office hysteroscopy (OH) on the subsequent frozen-thawed embryo transfer (FET) in infertile women who experienced a failed IVF-embryo transfer (IVF-ET) cycle. We included 577 infertile women who underwent OH because of a history of failed ET between October 2019 and September 2021. During OH, visible endometrial polyps (EPs) were diagnosed and removed by curette or biopsy forceps; chronic endometritis (CE) was diagnosed by histopathology and immunohistochemistry and treated with oral doxycycline (0.2 g/d) for 14 days. According to the hysteroscopic findings and endometrial pathology with immunohistochemistry, patients were divided into three groups: group A (n = 161) had CE with or without EPs, group B (n = 156) had EPs only, and group C (n = 260) had no CE or EPs. In the following FET cycle, the implantation rates were 47%, 51%, and 45% (P = 0.411); the clinical pregnancy rates were 56%, 62%, and 55% (P = 0.436); the live birth rates were 45%, 51%, and 42% (P = 0.205); and the miscarriage rates were 18%, 16%, and 22% (P = 0.497) in groups A, B, and C, respectively. There were no significant differences among groups (P > 0.05). OH is helpful for diagnosis and treatment of abnormal intrauterine environment in women with a failed IVF cycle and further improves their pregnancy outcome in the following FET.

Impact of thyroid autoimmunity on the cumulative live birth rates after IVF/ICSI treatment cycles

BackgroundCumulative live birth rate (CLBR) is considered as the most important endpoint for assessing the probability of having a baby in a complete in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycle. Many previous studies have focused on the association between thyroid autoimmunity (TAI) and live birth rate after first embryo transfer cycle, however, evidence on whether the presence of TAI affects the CLBR is lacking. The purpose of this study is to investigate the impact of TAI on the CLBR in a complete IVF/ICSI cycle.MethodsThis retrospective study included 12,796 women who underwent their first IVF/ICSI treatment between January 2019 and February 2021. Based on the levels of thyroid antibodies, 2,603 women were assigned to the TAI group, and 10,193 women were assigned to the control group. Subgroup analysis was performed according to the different causes of infertility (including male factor only, ovulation disorder, tubal factor, endometriosis and unexplained infertility) and different types and titres of thyroid antibodies. The primary outcome in this study was CLBR, which included live births from the fresh embryo transfer cycle and all subsequent frozen-thawed embryo transfer cycles performed before December 2021.ResultsThere was no significant difference in the CLBR between the TAI and control groups, even after adjusting for relevant confounders including age, body mass index, cause of infertility, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live birth: 50.6% vs. 52.1%, OR 0.94, 95% CI 0.86–1.02, adjusted OR 0.97, 95%CI 0.89–1.06). Subgroup analysis showed that no significant difference was observed in CLBR between the TAI and control groups for all causes of infertility, except for infertility attributed to endometriosis. Among women with endometriosis, the CLBR was significantly lower in the TAI group than that in the control group; however, this difference was not significant after adjusting for potential confounders including age, body mass index, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live births: 43.1% vs. 51.0%, OR 0.73, 95% CI 0.53–0.99, adjusted OR 0.74, 95% CI 0.53–1.02). Another subgroup analysis demonstrated that the type and titre of thyroid antibody did not affect CLBR in women with TAI.ConclusionsIn our study, there was no significant difference in the CLBR between women with TAI and those without TAI, which suggests that TAI did not affect the chances of having a baby in a complete IVF/ICSI treatment cycle.

Follitropin Alpha versus Follitropin Beta in IVF/ICSI Cycle: A Retrospective Cohort Study.

The purpose of this study was to compare the efficacy of Follitropin alpha (Gonal-F) and Follitropin beta (Puregon) on cumulative live birth rate (CLBR), defined as the percentage of the number of patients who delivered for the first time in a single ovarian stimulation cycle and the number of patients in all oocyte retrieval cycles. A retrospective cohort study including 2864 infertile patients who underwent ovarian stimulation with Puregon (group A, n=1313) and Gonal-F (group B, n=1551) was conducted between July 2015 and June 2021 at a university-affiliated reproductive medicine center. Reduce potential confounding factors between groups, propensity scores and multivariable logistic regression analyses were estimated to obtain unbiased estimates of outcomes. The primary outcome was the difference in CLBR between the two groups. Each group identified 1160 individuals after propensity score matching (PSM). Baseline characteristics were similar between groups after PSM. The total gonadotrophin (Gn) dose (2400 vs 2325), p=0.038) and cost of Gn usage (5327.9¥ vs 7547.2¥, p<0.001) between the Puregon and Gonal-F groups were statistically significant. Nevertheless, the pregnancy outcomes between the two groups were comparable after fresh embryo transfer and subsequent frozen-thawed embryo transfer. Additionally, there was also no difference observed in the primary outcome of CLBR (52.8% vs 55.7%, p=0.169). Multivariable regression analysis revealed that the type of Gn was not associated with CLBR (p = 0.912). Gonal-F may be a reasonable option for infertile patients who are hesitant to receive more Gn dosage injections. Furthermore, Puregon can eliminate unneeded anxiety and expenses while also administering more flexibility. Taken together, these findings could well be utilized in everyday clinical practice to better inform patients when deciding on an ovarian stimulation strategy.

Pregnancy outcomes after frozen-thawed embryo transfer in women with COVID-19 history: A prospective cohort study.

The clinical effect ofCoronavirus disease 2019 (COVID-19)on endometrial receptivity and embryo implantation remains unclear. Herein, we aim to investigate whether a COVID-19 history adversely affect female pregnancy outcomes after frozen-thawed embryo transfer (FET). This prospective cohort study enrolled 230 women who underwent FET cycles from December 2022 to April 2023 in an academic fertility center. Based on the history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection before FET, women were divided into the infected group (n = 136) and the control group (n = 94). The primary outcome was the clinical pregnancy rate per cycle. Multivariate logistic regression analysis was conducted to adjust for potential confounders, while subgroup analysis and restricted cubic splines were used to depict the effect of postinfection time interval on FET. The results showed that the clinical pregnancy rate was 59.6% in the infected group and 63.9% in the control group (p = 0.513). Similarly, the two groups were comparable in the rates of biochemical pregnancy (69.1% vs. 76.6%; p = 0.214) and embryo implantation (51.7% vs. 54.5%; p = 0.628). After adjustment, the nonsignificant association remained between prior infection and clinical pregnancy (OR = 0.78, 95% CI: 0.42-1.46). However, the odds for clinical pregnancy were significantly lower in the ≤30 days subgroup (OR = 0.15, 95% CI: 0.03-0.77), while no statistical significance was detected for 31-60 days and >60 days subgroups compared with the uninfected women. In conclusion, our findings suggested that SARS-CoV-2 infection in women had no significant effect on subsequent FET treatment overall, but pregnancy rates tended to be decreased if vitrified-thawed embryos were transferred within 30 days after infection. A 1-month postponement should be rationally recommended, while further studies with larger sample groups and longer follow-up periods are warranted for confirmation.

High prevalence of chronic endometritis is associated with metabolic abnormality and reduced live birth rate among IVF women with non-uniform endometrial echogenicity.

To assess the prevalence of chronic endometritis (CE) among women with non-uniform endometrial echogenicity, and to evaluate the association between CE and metabolic characteristics as well as pregnancy outcomes in the subsequent frozen-thawed embryo transfer (FET) cycles. Retrospective cohort study. University-based hospitals and an academic medical center. A total of 315 patients included in this research underwent hysteroscopy and endometrial biopsy before the first FET cycle after whole embryos freezing. Patients were divided into CE (histopathologic CE or hysteroscopic CE) and non-CE groups. Freeze-all strategy, hysteroscopy and endometrial biopsy. Baseline and cycle characteristics, hysteroscopic, and histopathological profile, as well as pregnancy outcomes. The prevalence of histopathologic CE and hysteroscopic CE were 78.1% and 34.9%, respectively. CE was associated with higher homocysteine level and BMI, independent of insulin response and dyslipidemia. High homocysteine level and BMI were risk factors for histopathologic CE (OR: 1.182; 95% CI: 1.01-1.384; p=.037) and hysteroscopic CE (OR: 1.117; 95% CI: 1.041-1.199; p=.002), respectively. Histopathologic CE was a risk factor for live birth (OR:2.167; 95% CI: 1.037-4.525; p=.04), and hysteroscopic CE was an independent risk factor for both live birth (OR: 4.239; 95% CI: 1.929-9.313; p=.001) and cumulative live birth (OR: 3.963; 95% CI: 1.875-8.376; p=.001). Infertile women with non-uniform endometrial echogenicity have a high prevalence of CE which significantly reduces the live birth rate. Diagnosing CE by hysteroscopy is important to assess the cumulative probability of pregnancy in IVF patients.

Segmented in vitro fertilization and frozen embryo transfer in levonorgestrel-releasing intrauterine device treated patients with endometrial cancer

PurposeTo evaluate the efficacy of levonorgestrel-releasing intrauterine device (LNG-IUD) during controlled ovarian stimulation (COS) in patients with early-stage endometrioid endometrial cancer (EEC).MethodsA retrospective study was conducted on patients with stage IA1 EEC who achieved complete response after fertility-sparing treatment from December 2018 to December 2021, with all the women who underwent COS having LNG-IUDs inserted in their uterine cavity.Results16 patients were enrolled who underwent 26 COS cycles and average age was 33.19 ± 4.04 years. 12 patients had 19 subsequent frozen-thawed embryo transfer (FET) cycles. Among the other four patients, no embryos were obtained in 1 patient, 1 patient got pregnancy spontaneously with term delivery after COS, 1 patient relapsed before FET, and 1 patient did not receive embryo transfer for personal reason. Among 19 FET cycles, the clinical pregnancy and live birth rates in each ET cycle were 36.84% (7/19) and 26.32% (5/19), respectively. 7 clinical pregnancies resulted in 2 miscarriages (28.6%), and 5 live births (71.4%). Totally 6 patients achieved 7 live births, and the cumulative live birth rate was 37.5% (6/16). Three (18.75%) out of 16 patients relapsed after COS during the follow-up period (31.31 ± 15.89 months) and two of them were initially diagnosed with moderately differentiated EEC. Time interval from COS to relapse was 6.63,11.67 and 16.23 months, respectively.ConclusionThe combination of LNG-IUD treatment and segmented IVF may be a viable treatment strategy to improve oncological and reproductive outcomes for patients with early-stage EEC.

Laparoscopy versus open surgery for the surgical management of tubo-ovarian abscess (TOA). Is there a beneficial impact of early endoscopic intervention in terms of fertility rates?

To compare success rates and complications in women undergoing laparoscopic versus open surgical management of tubo-ovarian abscess. We further examined whether early laparoscopic intervention has any impact on pregnancy rates in a subgroup of infertile patients following frozen-thawed embryo transfer. Hospital records of 48 patients diagnosed with TOA between January 2015 and December 2020, who underwent surgical intervention or received only medical treatment were analyzed. All patients were hospitalized, and parenteral antibiotics were commenced on admission initially. Laparoscopic or open surgery was performed within 48 hours course of intravenous antibiotherapy (early intervention) or later according to the clinical findings and antibiotherapy response. Of 48 patients with TOA, 18 (37.5%) underwent laparoscopic and 30 (62.5%) underwent open surgical intervention. The median postoperative hospital stay was shorter (4.5 days vs 7.5 days, respectively; p = 0.035), and postoperative opioid analgesic requirement was lesser in the laparoscopy group compared to open surgery group (22% vs 53%, respectively; p = 0.034). Intra- and post-operative complication rates were similar between the groups. Of these 48 patients, seven were diagnosed to have TOA following oocyte retrieval, and four of these conceived with frozen thawed embryo transfer all of whom underwent laparoscopic surgery within 48 hours of diagnosis. Minimal invasive surgery should be preferred even in the presence of severely adhesive and inflammatory TOA in order to improve postoperative outcomes. Moreover, early laparoscopic intervention may be considered in infertile patients with an aim to optimize pregnancy rates in a subsequent frozen-thawed embryo transfer.

Elective single versus double blastocyst-stage embryo transfer in women aged 36 years or older: a retrospective cohort study

We evaluated if elective single-blastocyst transfer (eSBT) could be adopted in women aged 36 or older. In this retrospective cohort, women aged ≥36 years received IVF ovarian stimulation cycles and had ≥ two blastocysts. A total of 240 women underwent eSBT and 189 double-blastocyst transfer (DBT) in the first transfer cycle. The subsequent frozen-thawed embryo transfer cycles were a combination of single- and double- blastocyst transfers. Analysis was stratified for patients in age groups 36–37, 38–39 and ≥40, considering the quality of the blastocyst transferred. The cumulative live birth rates (cLBR) were 74.2% (178/240) versus 63.0% (119/189) after eSBT versus DBT, respectively (aOR: 1.09 (0.68, 1.75)). Time to live birth did not vary significantly between the two groups (HR: 0.85 (0.68, 1.08)). The total number of children born was 194 after eSBT (162 singletons and 16 pairs of twins) versus 154 (84 singletons and 35 twins) after DBT. The odds ratios for preterm birth (0.37 (0.21–0.64)), and low birth weight (0.31 (0.16, 0.60)) were all lower in eSBT. In women aged ≥36 years, cLBR following single- versus double- blastocyst transfer was comparable while the odds of multiple live births and adverse perinatal outcomes were reduced.

Effects of time of recombinant luteinized hormone supplementation on pregnancy outcomes of women with advanced reproductive age during follicular-phase long protocol

Objective: To investigate the effects of supplementation of recombinant luteinized hormone (rLH) and its timing on pregnancy outcomes of patients at 35 years or older with follicular-phase long protocol. Methods: Clinical data of women undergoing in vitro fertilization or intracytoplasmic sperm injection with follicular-phase long protocol was collected and retrospectively analyzed in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2019. There were 558 patients at 35 years or older included in this study, and they were divided into three groups: group A was patients with only recombinant follicle stimulating hormone (rFSH) stimulation (127 cycles), group B was patients with rFSH plus rLH supplementation in the mid-follicular phase (141 cycles), and patients in group C received combined rFSH and rLH from the first day of ovarian stimulation (290 cycles). The basic characteristics of patients of each group were observed and the effects of ovarian simulation and pregnancy outcomes were compared among the three groups. Logistic regression model was performed to explore the association between different groups and pregnancy outcomes. Results: The basic characteristics such as age, duration of infertility, body mass index (BMI) and serum basic follicle stimulating hormone (FSH) were comparable among the three groups (all P>0.05). Anti-Müllerian hormone (AMH), antral follicles count (AFC) and basic luteinized hormone (LH) were significantly lower in group C compared to group A and group B (all P<0.05). There were statistically significant differences in initiation dosage, total dosage and duration of gonadotropin (Gn) among the three groups (all P<0.01), the initiation dosage, total dosage and duration of Gn were higher in group C than the other two groups. The number of oocytes retrieved and available embryos were significantly lower in group B and group C than group A (all P<0.001). In fresh embryo transfer cycles, significantly higher implantation rate (45.3%, 117/258) and clinical pregnancy rate (52.6%, 111/211) were found for group C when compared with group A and group B (P=0.036, P=0.006). The live birth rate in fresh embryo transfer cycles was comparable among the three groups (P=0.098). The implantation rate, clinical pregnancy rate and live birth rate in the subsequent frozen-thawed embryo transfer cycles did not differ significantly among the three groups (all P>0.05). There were no significantly differences in the cumulative pregnancy rate and the cumulative live birth rate among the three groups (all P>0.05). After adjusted for age, BMI, AMH, AFC, basic FSH and LH, total Gn dosage, endometrial thickness at transfer, number of oocytes retrieved, number of embryos transferred and stage of embryo transferred, in fresh embryo transfer cycles, the clinical pregnancy rate (adjusted OR=2.793, 95%CI: 1.512-5.162, P<0.001) and live birth rate (adjusted OR=2.324, 95%CI: 1.241-4.351, P=0.008) were higher in group C, while clinical pregnancy rate and live birth rate were similar between group B and group A in fresh embryo transfer cycles (all P>0.05); there was no significant difference in cumulative live birth rate among the three groups (P>0.05). Conclusions: The supplementation of rLH from the first day of ovarian stimulation improves the pregnancy outcomes of patients at 35 years or older in fresh embryo transfer cycles during follicular-phase long protocol. However, the supplementation of rLH has no benefit on cumulative live birth rate.

DIFFERENCES IN REPRODUCTIVE AND NEONATAL OUTCOMES BASED ON TIME INTERVAL FROM CESAREAN DELIVERY TO FROZEN EMBRYO TRANSFER

To determine if the interval between prior cesarean delivery (CD) and subsequent frozen-thawed embryo transfer (FET) impacts reproductive and neonatal outcomes following the use of assisted reproductive technologies.

The effect of coronavirus disease 2019 immunity on frozen-thawed embryo transfer cycles outcome

ObjectiveTo study the effect of patients’ immunization after coronavirus disease 2019 (COVID-19) infection or messenger ribonucleic acid (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine on frozen-thawed embryo transfer (FET).DesignCohort retrospective study.SettingTertiary university affiliated medical center.Patient(s)All consecutive patients undergoing FET cycles in our center. The study group (immune group) consisted of patients treated during the COVID-19 pandemic (between January 2021 and August 2021) who either recovered from COVID-19 infection or received the mRNA SARS-CoV-2 vaccine. The control groups consisted of patients treated during the COVID-19 pandemic (between January 2021 and August 2021) but were not infected or did not receive the mRNA SARS-CoV-2 vaccine (not-immune2021 group) and those treated between January 2019 and August 2019 (before the pandemic) (not-immune2019 group).Intervention(s)Frozen-thawed embryo transfer cycles.Main Outcome Measure(s)Ongoing pregnancy rates and FET cycles’ characteristics. Data on patient age and variables related to infertility treatment were collected from the patient records.Result(s)During the study periods, 428 patients underwent 672 FET cycles. The immune group consisted of 141 patients who underwent 264 FET cycles (44 in postinfection and 220 in postvaccination), whereas the not-immune2021 and not-immune2019 groups consisted of 93 and 194 patients undergoing 125 and 283 FET cycles, respectively. Patients’ characteristics and the types of endometrial preparations were comparable between the study groups. The implantation rate and clinical and ongoing pregnancy rates per transfer were similar between the study groups (immune group, postinfection and postvaccination; not-immune2021 group; not-immune2019 group).Conclusion(s)Coronavirus disease 2019 infection or vaccination did not affect patients’ performance or implantation in their subsequent FET cycle.

Lifestyle intervention prior to IVF does not improve embryo utilization rate and cumulative live birth rate in women with obesity: a nested cohort study.

Lifestyle intervention prior to IVF does not improve embryo utilization rate and cumulative live birth rate in women with obesity: a nested cohort study.

P–633 lifestyle intervention prior to IVF does not improve embryo utilization rate and cumulative live birth rate in women with obesity

Abstract Study question Does lifestyle intervention prior to in vitro fertilization (IVF) improve embryo utilization rate (EUR) and cumulative live birth rate (CLBR) in women with obesity? Summary answer A six-month lifestyle intervention preceding IVF improved neither EUR, nor CLBR in women with obesity. What is known already A randomized controlled trial (RCT) evaluating the efficacy of a low caloric liquid formula diet (LCD) preceding IVF in women with obesity was unable to demonstrate an effect of LCD on embryo quality and live birth rate. In that study, only one fresh embryo transfer (ET) or, in case of freeze-all strategy, the first transfer with frozen-thawed embryos was reported. We hypothesized that any effect on embryo quality of a lifestyle intervention in women with obesity undergoing IVF treatment is better revealed by EUR and CLBR after transfer of fresh and frozen-thawed embryos. Study design, size, duration This is a nested cohort study within an RCT. The LIFEstyle study examined whether a six-month lifestyle intervention prior to assisted reproductive technology (ART) in women with obesity improved live birth rate, compared to prompt ART within 24 months after randomization. In the original study, 577 women with obesity and infertility were assigned to a lifestyle intervention followed by ART (N = 290) or to prompt ART (N = 287) between 2009 and 2012. Participants/materials, setting, methods The first IVF cycle with successful oocyte retrieval was included, resulting in 51 participants in the intervention group and 72 in the control group. EUR was defined as the proportion of inseminated/injected oocytes that could be transferred or cryopreserved as an embryo. Analysis was performed per cycle and per oocyte/embryo. CLBR was defined as the percentage of participants with at least one live birth from the first fresh and subsequent frozen-thawed ET(s). Main results and the role of chance The overall mean age was 31.64 years, and the mean BMI was 35.40 ± 3.21 kg/m2 in the intervention group, and 34.86 ± 2.86 kg/m2 in the control group (P = 0.33). The mean difference of weight change at six months between the two groups was in favor of the intervention group (mean difference in kg: –3.14, 95% CI: –5.73 – –0.56). The median (Q25; Q75) of EUR was 33.3% (12.5; 60.0) in the intervention group and 33.3% (16.7; 50.0) in the control group in the per cycle analysis (adjusted B: 2.7%, 95% CI: –8.6 – 14.0). In the per oocyte/embryo analysis, in total 280 oocytes were injected or inseminated in the intervention group, 113 were utilized (transferred or cryopreserved embryos, EUR = 40.4%); in the control group EUR was 30.8% (142/461). The lifestyle intervention did not significantly improve EUR (adjusted OR: 1.36, 95% CI: 0.94 – 1.98) in the per oocyte/embryo analysis taking into account the interdependency of the oocytes per participant. CLBR was not significantly different between the intervention group and the control group after adjusting for type of infertility (male factor and unexplained) and smoking (27.5% vs 22.2%, adjusted OR: 1.03, 95% CI: 0.43 – 2.47). Limitations, reasons for caution This study is a nested cohort study within an RCT, and no power calculation was performed. The randomization was not stratified for indicated treatment. The limited absolute weight loss and the short duration of the lifestyle intervention might be insufficient to affect EUR and CLBR. Wider implications of the findings: Our data do not support the hypothesis of a beneficial effect of lifestyle intervention on embryo quality and CLBR after IVF in women with obesity. Trial registration number NTR 1530

P–774 Clinical effectiveness of elective single versus double blastocyst transfer in women aged 36 years or older

Abstract Study question If the elective single-blastocyst transfer (eSBT) strategy can be applied to women aged 36 or older. Summary answer In women ≥36 years old with at least two blastocysts, eSBT increased cumulative livebirth rate (LBR) while minimizing twins compared with double blastocyst transfer (DBT). What is known already: In young women with a good prognosis, eSBT policy is an accepted strategy to maintain LBR while decreasing multiple gestation. However, in many areas of the world DBT is still applied in older women. Study design, size, duration We performed a retrospective cohort study of 429 women aged ≥36 years or older who received IVF ovarian stimulation cycles between Jan 2015 and Oct 2018 and who had at least two blastocysts. Women were followed up until Oct 2020 for their fertility outcomes including cumulative live birth and multiple pregnancies. The study was performed at the Northwest Women and Children’s Hospital, Xi’an, China. Participants/materials, setting, methods Out of 429 women, 240 underwent a fresh cycle of eSBT and 189 DBT. The subsequent frozen-thawed embryo transfer cycles were a combination of single- and double- blastocyst transfers, more commonly the latter. Analysis was stratified for patients in age groups 36–37, 38–39 and ≥40 and quality of the blastocyst transferred, as graded by morphological examination. Outcomes were the LBR in the fresh cycle, cumulative LBR and multiple rate after fresh and frozen embryo transfers. Main results and the role of chance The cumulative LBR was 74.2% (178/240) for eSBT versus 63.0% (119/189) for DBT (OR = 1.69, 95%CI 1.12–2.56), irrespective of female age. The multiple rate was 9% (16/178) after eSBT versus 29.4% (35/119) after DBT (P- value &amp;lt; .001). The total number of children born was 194 after eSBT versus 154 after DBT. Stratified by female age, the cumulative LBRs in women aged 36–37 (78.9 vs 70.5%), 38–39 (68.9 and 61.1%) and ≥ 40 years (59.3 and 47.5%), were higher after eSBT compared with DBT, however, the differences did not reach statistical significance in each subgroups. LBRs in the fresh cycles were comparable for patients with eSBT compared with DBT (52.1% vs. 52.4%, OR = 0.99, 95%CI 0.68–1.45). In women &amp;lt; 40 years, DBT resulted in a small non-significant increase in LBR in the fresh transfer (63.2% vs. 61.2%, 95%CI=0.64–1.85, 36–37 years; 48.1% vs. 41.0%, 95%CI=0.64–2.80, 38–39 years) at the expense of a marked increase in twinning rate (0–5.4% vs. 31.7–34.6%). For women ≥40 years, no significant differences were observed in the LBR (37.0% vs 45%, 95%CI 0.47–4.07) or twinning rate (0 vs 7.7%) between eSBT and DBT group. The findings persisted with and without accounting for quality of the blastocyst transferred. Limitations, reasons for caution This study is limited by its observational character. Wider implications of the findings: In women ≥36 years with two blastocysts, eSBT should be the preferred treatment which maximizes the cumulative LBR for a decrease in the rate of multiple pregnancies. Trial registration number Not applicable

P–700 Increased progesterone to mature oocyte index is associated with lower top-quality embryo rate in GnRH antagonist protocols

Abstract Study question Do progesterone elevation (PE) on trigger day and progesterone to mature oocyte index (PMOI) affect embryo quality and the chance of live birth? Summary answer The top-quality embryo rate is decreased by increasing PMOI, but it has no association with absolute serum progesterone levels. What is known already Progesterone elevation have been reported to significantly decrease pregnancy and implantation rates. The main mechanism of this adverse effect is mainly related to an asynchrony between the endometrium and the embryo. Many of the previous studies have failed to show a significant impact of PE on embryo quality and the success of subsequent frozen-thawed embryo transfer (FET) cycle. However, PMOI was suggested to be more predictive than PE of ART outcome and might be associated with embryo quality. Study design, size, duration A single-centre retrospective cohort study was conducted. All FET cycles performed in a university hospital infertility centre between January 2016 and December 2019 were reviewed. A total of 44 patients who had PE (&amp;gt;1.5 ng/ml) on trigger day and 134 patients who did not have PE were assessed. Participants/materials, setting, methods The study group consisted of patients who had PE (&amp;gt;1.5 ng/mL) during fresh COS cycle and the control group consisted of patients who did not have PE. In addition to effect of PE on subsequent FET cycle outcome, an association between PMOI and embryo quality was assessed. The threshold level to define increased PMOI (&amp;gt;0.12 ng/ml) was calculated as the median level of the whole study cohort. Main results and the role of chance The mean ages of the study and control groups were 30.4±5.4 years and 31.1±5.6 years, respectively (P = 0.413). Although the number of oocytes collected and MII oocytes were significantly higher in patients with PE, the total number of frozen embryos were similar between the groups. There were no significant differences concerning the outcome measures including live birth rate in the subsequent FET cycle between participants with and without PE (27.3% vs. 23.9%, respectively; P = 0.652). The rate of top-quality embryos was similar between participants with and without PE (43% vs. 52%, respectively; P = 0.370). However, the rate of top-quality embryos was significantly lower in cycles with PMOI&amp;gt;0.12 ng/ml than in cycles PMOI&amp;lt;0.12 ng/ml (42% vs. 56%, respectively; P = 0.027). Limitations, reasons for caution The retrospective design and the small sample size derived from a single institution. Wider implications of the findings: Increased PMOI, which is associated to lower top-quality embryo rate, may in turn result in diminished cumulative live birth rate. Trial registration number Not applicable

Granulocyte Colony-Stimulating Factor Combined With Transcutaneous Electrical Acupoint Stimulation in Treatment of Unresponsive Thin Endometrium in Frozen Embryo Transfer Cycles.

Objective: This trial was designed to assess the treatment effects of granulocyte colony-stimulating factor (G-CSF) and transcutaneous electrical acupoint stimulation (TEAS) on thin endometrium in frozen-thawed embryo transfer (FET) cycles.Methods: Ninety-nine patients with previous cancellations of embryo transfer were included, 56 of whom were prospectively treated with intrauterine perfusion of G-CSF in subsequent FET cycles. The selected patients were randomized into the G-CSF perfusion only group and the G-CSF perfusion combined with TEAS group. The other 43 patients were retrospectively included as controls.Results: Compared to previous cycles, endometrial thickness was statistically significantly increased in the two treatment groups (5.97 ± 0.60, 7.52 ± 0.56, 6.14 ± 0.52, and 7.66 ± 0.44; P = 0.00 and 0.00, respectively). The increases in endometrial thickness suggested that no statistically significant difference was found between the two treatment groups. The G-CSF with TEAS group suggested a higher embryo implantation rate than the G-CSF perfusion only and control groups (33.33 and 29.1% and 33.33 and 17.39%; P = 0.412 and 0.091, respectively). The G-CSF combined with TEAS group demonstrated nominally higher clinical and ongoing pregnancy rates than the G-CSF perfusion-only group and controls, though, the difference was not statistically significant.Conclusion: G-CSF has a potential role in improving endometrium thickness in patients with thin unresponsive endometrium in FET treatment cycles. In addition, when combined with TEAS, G-CSF perfusion treatment also improves the embryo implantation rate; however, randomized controlled trials are highly demanded to provide high-grade evidence regarding clinical pregnancy rate after G-CSF perfusion treatment.

Granulocyte-Macrophage Colony Stimulating Factor in Single Blastocyst Conditioned Medium as a Biomarker for Predicting Implantation Outcome of Embryo.

BackgroundIt is highly desirable to develop new strategies based on secretomics to more accurately selection of embryos with the highest developmental potential for transfer. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to promote embryo development and pregnancy establishment. However, the predictive value of GM-CSF in single blastocyst selection remains unclear. This study is to determine the concentration of GM-CSF in human single-blastocyst conditioned medium (SBCM) and to evaluate its association with embryo quality and pregnancy outcome.MethodsThe patients with ≤38 years of age receiving the first cycle of assisted reproductive therapy were included in this study. The patients who had <4 top-quality embryos formed by the fertilized two pronuclear zygotes on day 3 were excluded. A total of 126 SBCM samples (SBCMs) were included, of which blastocysts from 77 SBCMs were later transferred in subsequent frozen-thawed embryo transfer. The concentrations of GM-CSF were detected by single-molecule array (SIMOA) and analyzed for their possible association with embryo quality and pregnancy outcomes. The top-quality embryo (TQ), positive HCG (HP), clinical pregnancy (CP), and ongoing pregnancy (OP) rates were determined and compared between groups divided based on GM-CSF concentrations.ResultsThe detection rate of GM-CSF was found to be 50% in all SBCMs. There were significant differences in TQ rate, HP rate, CP rate and OP rate among high concentration group, medium concentration group and low concentration group. Both GM-CSF alone or GM-CSF combined with the morphological score (MS) had a greater AUC of ROC curve than that of MS alone to predict the pregnancy outcome, and GM-CSF combined with MS had the highest AUC.ConclusionsThe concentration of GM-CSF in SBCM was detected at fg/ml levels, which was associated with embryo quality and pregnancy outcome. Collectively, GM-CSF may be used as a biomarker for prediction of pregnancy outcome and selection of embryos with high developmental potential for transfer in assisted reproductive technology (ART).

Predicting the Likelihood of Live Birth in Assisted Reproductive Technology According to the Number of Oocytes Retrieved and Female Age Using a Generalized Additive Model: A Retrospective Cohort Analysis of 17,948 Cycles.

CapsuleWe designed a predictive reference model to evaluate how many stimulation cycles are needed for a patient to achieve an ideal live birth rate using assisted reproductive technology.ObjectiveTo develop a counseling tool for women who wish to undergo assisted reproductive technology (ART) treatment to predict the likelihood of live birth based on age and number of oocytes retrieved.MethodsThis was a 6-year population-based retrospective cohort analysis using individual patient ART data. Between 2012 and 2017, 17,948 women were analyzed from their single ovarian stimulation cycle until they had a live birth or had used all their embryos. All consecutive women between 20 and 49 years old undergoing their ovarian stimulation cycles for ART in our center were enrolled. The cumulative live birth rate (CLBR) was defined as the delivery of a live neonate born during fresh or subsequent frozen–thawed embryo transfer cycles. Only the first delivery was considered in the analysis. Binary logistic regression was performed to identify and adjust for factors known to affect the CLBR independently. A generalized additive model was used to build a predictive model of CLBR according to the woman’s age and the number of oocytes retrieved.ResultsAn evidenced-based counseling tool was created to predict the probability of an individual woman having a live birth, based on her age and the number of oocytes retrieved in ART cycles. The model was verified by 10 times 10-fold cross-validation using the preprocessed data, and 100 area under the curve (AUC) values for receiver operating characteristic (ROC) curves were obtained on the test set. The mean AUC value was 0.7394. Our model predicts different CLBRs ranging from nearly 90% to less than 20% for women aged 20–49 years with at least 22 oocytes retrieved. The CLBRs of women aged 20–28 years were very similar, nearly on one trend line with a certain number of oocytes retrieved. Differences in the CLBR began to appear by the age of 29 years; these increased gradually in women aged >35 years.ConclusionA predictive model of the CLBR was designed to serve as a guide for physicians and for patients considering ART treatment. The number of oocytes needed to be retrieved to achieve a live birth depends on the woman’s age.

HCG day progesterone level has no impact on the frozen thawed embryo transfer cycle outcome

ObjectiveTo assess the association between hCG day progesterone levels and subsequent frozen-thawed embryo transfer (FET) cycle outcome in infertile women with and without polycystic ovary syndrome (PCOS). MethodData of 178 women who underwent FET at a university-based infertility clinic between January 2016 and December 2019 were reviewed. The study group consisted of women who had progesterone elevation (PE) during fresh controlled ovarian stimulation (COS) cycle. A sub-group analysis was also performed in PCOS and non-PCOS patients. ResultsThere were no differences in clinical pregnancy (47.7 % vs. 50.7 %, p = 0.729), miscarriage (15.9 % vs. 22.4 %, p = 0.359), and live birth rates (27.3 % vs. 23.9 %, p = 0.652) following FET between women with and without PE in the fresh cycle. The results remained non-significant regarding the clinical pregnancy (46.7 % vs. 53.4 %, p = 0.549), miscarriage (13.3 % vs. 27.6 %, p = 0.133), and live birth rates (26.7 % vs. 19.0 %, p = 0.408) in participants with PCOS (n = 88). ConclusionhCG day progesterone level in the fresh COS cycle does not have a significant impact on the subsequent FET cycle neither in PCOS nor in non-PCOS women.