Similar Live Birth Rates Research Articles

P-586 Adding letrozole to gonadotropins during ovarian stimulation for IVF results in a similar cumulative live birth rate at lower costs following a failed IVF cycle

Abstract Study question Following a failed IVF cycle, does adding letrozole for the first 5 days of a repeated cycle have any advantage versus repeating the same protocol? Summary answer Following a failed IVF cycle, letrozole supplementation during ovarian stimulation for IVF results in a similar cumulative live birth rate (CLBR) with 22% less gonadotropins. What is known already Letrozole results in an increase of intraovarian androgen concentration, which augments follicular stimulating hormone (FSH) receptor expression on granulosa cells and follicular responsiveness to exogenous gonadotropins. Letrozole co-treatment with gonadotropins during controlled ovarian stimulation (COH) for IVF has been investigated mainly in poor and normo-responders with conflicting clinical outcomes. This is the first and largest study that investigates the effects of adding letrozole for the first five days of COH for IVF, in GnRH antagonist cycles, to a category of patients who had a prior failed stimulated IVF cycle using the same protocol. Study design, size, duration This is retrospective monocentric study of 426 patients, with a prior failed stimulated IVF cycle using an antagonist protocol, who underwent a second cycle between 2012 and 2017. In those patients, we studied the clinical outcomes of doing a repeated cycle, using the same protocol with the addition of 5mg of letrozole daily in the first 5 days of the cycle (Group A, N = 213) versus doing a repeated similar cycle without letrozole (Group B, N = 213). Participants/materials, setting, methods Groups A and B were matched for age, body mass index, anti-mullerian hormone and infertility diagnosis. Statistical analyses were carried out using student t test, Anova and linear regression models. The primary outcome was the CLBR. Secondary outcomes included the number of mature follicles, the number of mature oocytes (MII), the number of usable embryos, clinical pregnancy rates (CPR), live birth rates (LBR) and the total dose of gonadotropins administered. Main results and the role of chance This is the first study that investigates the effects of co-treatment with letrozole during COH for IVF in the category of patients who had a prior failed IVF cycle. Our results show that patients who received letrozole during COH with gonadotropins, versus gonadotropins alone, had a significantly lower number of MII oocytes (7±4.6 vs 8,2±5.0; P < 0.01). However, despite that, they had a similar number of usable embryos (1.8±1.6 vs 1.9±1.7; P = 0.31), CPR (23.5% vs 28.7%; p = 0.22), LBR per embryo transfer (16.9% vs 22.1%; p = 0.17) and CLBR (27.8% vs 25.3%; p = 0.55). A 22% lower dose of gonadotropins (3468±1389IU vs 4442±1657IU; p < 0.001) was needed to achieve similar pregnancy outcomes in the letrozole group versus the control group, resulting in lower treatment costs. Limitations, reasons for caution The retrospective nature of this study is its main limitation. Wider implications of the findings This study confirms that in women with a prior failed IVF cycle, co-treatment with letrozole results a similar cumulative live birth rate at a significant lower cost. Trial registration number NCT05677828

O-198 Obstetric and neonatal outcomes after natural frozen embryo transfer; results from a follow-up study of the Antarctica-2 RCT

Abstract Study question Do obstetric and neonatal outcomes of women who conceived through home-based monitoring of the ovulation in natural cycle frozen embryo transfer (NC-FET) differ compared to hospital-controlled monitoring of the ovulation in NC-FET using a hCG trigger? Summary answer We found no differences in obstetric and neonatal outcomes when home-based monitoring versus hospital-controlled monitoring of the ovulation in women undergoing NC-FET. What is known already NC-FET is associated with lower risk of adverse obstetric and neonatal outcomes compared with artificial cycle FET. The question of how to prepare the endometrium for FET, has now gained even more importance and taken on the dimension of safety into account as it should not simply be reduced to the basic question of effectiveness. Study design, size, duration Between April 10, 2018 and April 13, 2022, 1464 women were included in the Antarctica-2 RCT (n = 732 home-based monitoring and n = 732 hospital-controlled monitoring). For this study we performed a follow-up study in order to investigate obstetric and neonatal outcomes of the participating women with live births after the Antarctica-2 trial. Participants/materials, setting, methods We included only singleton livebirths. Main outcomes were gestational age, preterm birth (PTB), very preterm birth (very PTB), birth weight, large for gestational age (LGA) and small for gestational age (SGA). Additional outcomes included: gestational diabetes (GDM), hypertensive-disorders-of-pregnancy (HDP), pre-eclampsia (PE), abnormal placentation (including placenta previa and accrete), hospital admission during pregnancy, congenital anomalies and neonatal death. We calculated risk ratios and absolute risk differences (95% CI) using per protocol analysis. Main results and the role of chance Both studyarms resulted in similar live birth rates. Singleton live birth occured in 146 of 732 women (19.9%) following home-based and in 148 of 732 women (20.2%) following hospital-controlled monitoring. The mean gestational age in weeks was 39.0 (SD 0.3) for the home-based monitoring group versus 39.3 (SD 0.2) for the hospital-controlled monitoring group. We found no significant differences in preterm birth (5/146 versus 11/148, RR 1.00, 95% CI 0.90 – 1.10) or very preterm birth (1/146 versus 2/148, RR 1.00, 95% CI 0.90 – 1.10) for home-based versus hospital-based monitoring. Very preterm birth only occurred once in the home-based monitoring group. The mean birth weight was 3504.0 (SD 47.7) for the home-based monitoring group versus 3532.1 (SD 48.1) for the hospital-controlled monitoring group. We found no significant differences in LGA (20/146 versus 18/148, RR 1.00, 95% CI 0.90 – 1.10) and SGA (12/146 versus 12/148, RR 1.00, 95% CI 0.90 – 1.10) for home-based versus hospital-based monitoring. Also, no differences were found in HDP, PE, abnormal placentation, GDM, hospital admission during pregnancy and congenital anomaly. One neonatal death due to pulmonary hypoplasia occurred in the home-based monitoring group after very PTB. Limitations, reasons for caution The outcomes of HDP, PE, abnormal placentation, GDM and hospital admission during pregnancy were patient-reported and confirmed by hospital-files after contacting the participating centers. Wider implications of the findings NC-FET is the preferred treatment in women with ovulatory cycles undergoing FET. When home-based monitoring is compared to hospital-controlled monitoring in NC-FET we found no difference in obstetric or neonatal outcomes. Trial registration number not applicable

P-626 Time interval between ovulation triggering and oocyte retrieval and ART outcomes: an updated meta-analysis

Abstract Study question To explore whether prolonged hCG-ovum pickup(hCG-opu) interval improves assisted reproductive technology outcomes. Summary answer The clinical pregnancy rates can be increased by prolonging the hCG-opu interval, which would help develop more reasonable time schedules for fertility centers and patients. What is known already hCG-OPU interval greatly affects ART success, which allows to obtain the maximum number of competent mature oocytes while avoiding spontaneous ovulation. There is also no consensus regarding the optimal time between hCG-OPU, which some studies had shown that ideal ART outcomes could be obtained when oocyte retrieval was done more than 36 h -39 h after hCG priming, while others have concluded that an interval of more than 36 hours does not improve ART outcomes. Study design, size, duration CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science up to February 7, 2022 were searched for studies reporting associations between hCG-ovum pickup intervals and assisted reproductive technology outcomes. We searched for prospective or retrospective cohort studies measuring the hCG-OPU interval, using 36 hours as the cutoff value between short and long intervals. A combination of the following key search terms was used: “oocyte retrieval,” “human chorionic gonadotropin,” and “interval.” Participants/materials, setting, methods Studies analyzing the relationship between the hCG-OPU interval and ART outcomes were considered eligible for abstract screening. Intervention types included short (≤36 h) and long (>36 h) hCG-ovum pickup intervals in assisted reproductive technology cycles. All outcomes were based upon only fresh embryo transfers. Data were pooled using random-effects models. Heterogeneity was assessed using the I 2 statistic. Main results and the role of chance 12 studies were included in the meta-analysis, including five retrospective cohort studies, one prospective cohort study, and six randomized or quasi-randomized controlled trials. The short and long interval groups had similar oocyte maturation rates, fertilization rate and high-quality embryo rate (OR, 0.69; 95% CI, 0.45–1.06; I2 = 91.1%, OR, 0.88; 95% CI, 0.77–1.0; I2 = 44.4% and OR, 1.05; 95% CI, 0.95–1.17; I2 = 8.6%, respectively). The clinical pregnancy rates in the long retrieval group were significantly higher than in the short retrieval group (OR, 0.66; 95% CI, 0.45–0.95; I2 = 35.4%). The groups had similar miscarriage and live birth rates (OR, 1.92; 95% CI, 0.66–5.60; I2 = 0.0% and OR, 0.50; 95% CI, 0.24–1.04; I2 = 0.0%, respectively). Limitations, reasons for caution Using studies without patient data represents a potential source of bias. The hCG-OPU intervals were selected based on clinical relevance, resulting in statistical heterogeneity. Despite sensitivity analysis, such heterogeneity sources call for caution when interpreting the results. Wider implications of the findings The clinical pregnancy rates can be increased by prolonging the hCG-OPU (>36h), which would support the search for better clinical outcomes. The finding should be validated. And if validated by multicenter, randomized, controlled trials, long interval could be implemented in ART programs, resulting in better clinical pregnancy outcomes. Trial registration number not applicable

P-184 Morphokinetic analysis of cases with vitrified-warmed oocytes in oocyte donation program

Abstract Study question Does vitrification of oocytes in oocyte donation program alter the morphokinetic pattern of human embryos? Summary answer Both the extrusion of the second polar body (tPB2) and the appearance of the pronuclei (tPNa) occur earlier in vitrified oocytes without affecting further development. What is known already Vitrification of oocytes has been a breakthrough in oocyte cryopreservation and significantly altered practices in IVF labs. Oocyte vitrification/warming has become an integral part of daily routine and thorough assessment of its efficiency is crucial. Though, studies of vitrified-warmed oocytes have shown similar fertilization, cleavage, blastulation, pregnancy and live birth rates to fresh oocytes, the morphokinetic pattern of embryos originating from vitrified oocytes has not been thoroughly studied. According to some studies vitrification may be related to delayed blastocyst formation while others failed to see any alteration in the morphokinetic pattern between embryos derived from fresh or frozen oocytes. Study design, size, duration This retrospective observational study was performed at Embryolab Fertility Clinic, in Thessaloniki, Greece between April 2020 and September 2021 and included 590 vitrified oocytes from 68 oocyte donation cycles. Control group consisted of 31 good prognosis cases (oocyte donation cycles or homologous oocyte cycles of women under 35 years old). Participants/materials, setting, methods 68 vitrified oocyte donation cycles and 31 fresh control cycles were analyzed. All oocytes after ICSI were cultured in Embryoscope time-lapse incubator up to blastocyst stage. Key time parameters and dynamic events were analyzed using generalized estimating equations (GEE) regression analysis for the non-independent nature of the data. Moreover, the following comparisons were performed between groups: fertilization, cleavage, top cleavage, blastocyst, top blastocyst and pregnancy rates. Main results and the role of chance There was no significant difference in fertilization rates between control and frozen oocytes (77.79% ± 15.73 vs 71.26% ± 21.50 respectively, p = 0.15). Cleavage rate and top cleavage rate (more than 6 cells, equal size, with no or minor fragmentation), were higher in frozen oocytes with this difference being significant (p = 0.02 for cleavage rate and p = 0.015 for top cleavage rate). Blastocyst rate and top blastocyst (2AA, 3AA, 3AB, 4AA, 4AB according to Gardner criteria) rate, though, showed similar rates with no statistically significant difference (Blastocyst rate: 74,15% ± 17.19-control vs 76.42% ± 30.75-frozen oocytes, p = 0.6 & Top blastocyst rate: 45.54% ± 24.04-control, 45.30% ± 32.04-frozen oocytes, p = 0.82). Pregnancy rates were not significantly different (control:85.19%, frozen oocytes:75.38%, p = 0.29). The comparison for key time parameters and dynamic events that were analyzed (tPB2, tPNa, tPNf, t2, t3,t4, t5, t6, t7, t8, t9+, tSC, tM, tSB, tB, tEB, S2, S3, S5, CC1, CC2, CC3,Compaction and Blastulation) showed significant difference in 2 time parameters: tPB2 (4.62 hours-control, 3.67 hours-frozen, Coef: -1.09, p = 0.015) and tPNa (9.07 hours-control, 8.25 hours-frozen oocytes, Coef: -1.06, p = 0.043). Limitations, reasons for caution The fact that the oocytes under comparison were not sibling as well as its retrospective nature, constitute the main limitations of the present study. Moreover, the number of cases included in this study was limited and the available information about ongoing pregnancy and live births is still pending. Wider implications of the findings tPB2 and tPNa seem to occur earlier in vitrified oocytes without affecting further development, implying a need for reviewing timings between OPU/vitrification/warming/ICSI. Moreover, vitrified oocytes displayed higher cleavage and top cleavage rates with unaffected blastocyst or pregnancy rates. Overall, vitrification of oocytes seems to be safe and reliable. Trial registration number N/A

P-636 Euploid blastocysts obtained in advanced maternal age women either in donor or autologous egg cycles showed similar live birth rates: a retrospective cohort study

Abstract Study question Do euploid blastocysts have the same implantation and live birth rate in autologous and donor egg cycles in patients with advanced maternal age (AMA)? Summary answer Euploid blastocysts transferred in AMA patients showed that implantation and live birth rates (LBR) were not significantly different between reproductively younger and older women. What is known already Aneuploidy rates increase steadily with age, reaching >80% in women >42 years old. The high prevalence of aneuploidies may provide an explanation for the low LBR achieved by assisted reproductive treatments, especially for women with AMA. Similarly, among oocyte donors, age is critical to achieving reproductive success independently of the recipients’ age. In donor cycles, recipients using oocytes from older donors had a statistically significantly lower LBR than younger donors. Currently, it still remains unclear whether the LBR differs between young donors versus old infertile patients in the context of euploid blastocyst transfers. Study design, size, duration Multicenter retrospective study with the preimplantation genetic test for aneuploidies (PGT-A) in both autologous and donor oocytes cycles between January 2018 and January 2021 was conducted at three different institutions (IVI-RMA, GeneraLife and Humanitas Fertility Center). 556 patients were included and matched 1:1 for the age of recipients, euploid blastocyst morphological quality, and day of development. In the frozen embryo transfers, endometrial preparation was done using hormonal replacement therapy (HRT) or natural cycles (NC). Participants/materials, setting, methods AMA patients older than 39 years underwent IVF. 556 patients who underwent autologous or donor oocyte cycles with at least one euploid blastocyst transferred were matched for oocyte age, blastocyst morphological quality and day of development. Blastocyst ploidy was assessed by aCGH or NGS analysis. Patients with uterine pathologies reported in the dataset were excluded. The primary outcome was LBR per first euploid blastocyst transfer. Outcomes were adjusted for confounders via logistic regression analyses. Main results and the role of chance 278 single euploid blastocysts tested by PGT-A were transferred in both autologous and donor oocyte cycles. No statistical differences were reported in the maternal age at transfer in the two groups (41.91 ± 2.03 and 41.75 ± 1.98, p = 0.55), endometrial thickness [(8.67, 95%CI: 8.45-8.88) and (8.36, 95%CI: 8.05-8.67)] and type of endometrial preparation (HRT or NC). Implantation rate and pregnancy rate were similar without statical difference in autologous or donor cycles, respectively [57.91%, (95%CI: 51.87-63.78) versus 56.83%, (95%CI: 50.79-62.74); p = 0.99)] and N = 158/278 (56.83%, 95%CI: 50.79-62.74) versus N = 161/278 (57.91%, 95%CI: 51.87-63.78), p = 0.86. The rate of ectopic pregnancy was not statistically different in both arms. Even the miscarriage rate was comparable in autologous N = 46/158, 16.55% (95%CI:12.38-21.45) versus donor group N = 45/161, 16.19%, (95%CI:12.06-21.05); p = 0.98. The LBR was not statistically different in autologous N = 111/278 (39.93%, 95%CI:34.13-45.95) and donor group 114/278 (41.01%, 95%CI:35.17-47.04), p = 0.86. No statistical difference was reported for gestational age and birthweight at delivery. The logistic regression analyzed as putative confounders: oocyte age, number of inseminated MII-oocytes, zygotes and euploid blastocysts, sperm parameters, endometrial preparation and endometrial thickness showed no statistical differences. Limitations, reasons for caution Despite the matched design, the retrospective nature is the major limitation of this study. Also, patients received PGT-A using NGS and CGH arrays technology. The aCGH analysis is less sensitive than more recent NGS technology. Lastly, the prevalence of adenomyosis could be underestimated due to retrospective data collection. Wider implications of the findings The dramatic decline in IVF treatment success is primarily caused by aneuploidies. Euploid blastocysts show LBR largely independent of oocyte age. Our study suggests no uterine effect of aging. The reproductive decline in women is mainly related to meiotic failure, therefore future insights should develop strategies to overcome chromosomal aneuploidies. Trial registration number NA

P-134 An artificial intelligence method based on time-lapse images and deep learning may predict if a day2/3 embryo will form a utilizable blastocyst

Abstract Study question Can iDAScore v2.0 predict likelihood of development into a utilizable blastocyst from time-lapse images captured during the first two or three days of embryo development? Summary answer iDAScore v2.0 predicts utilizable blastocyst formation from time-lapse images of early embryo development. Specific score thresholds can be established to ensure high specificity of prediction. What is known already Treatment efficacy would benefit from a reliable method to predict the potential of early embryos to develop into utilizable blastocysts and select fresh IVF treatment cycles suitable for blastocyst culture. Reports indicate that time-lapse images captured during the first few days of development and analyzed by deep learning methods may be an accurate approach. A fully automated AI model, iDAScore, is reported to be more accurate than routine morphology and morphokinetics for prediction of implantation. However, the applicability of iDAScore calculated on day 2 and 3 as a tool to predict blastocyst development has yet to be tested. Study design, size, duration This is a retrospective multicenter cohort study including time-lapse videos of 9111 embryos cultured to blastocyst stage, from 1283 fresh IVF treatments between 2016-2021 at two ART clinics together performing > 2000 OPU per year. Images captured during the first days of culture were used to calculate iDAScores (at 48 and 66 hours post insemination) and determine the ability to discriminate embryos likely to develop into utilizable blastocysts according to Gardner score of 3BB or more. Participants/materials, setting, methods Patients were required to be undergoing IVF treatment using their own (autologous) oocytes whereby all zygotes were cultured up to the blastocyst stage in GTL® culture medium using the Embryoscope+® time-lapse system (Vitrolife, Gothenburg, Sweden). At least two experienced embryologists graded blastocysts on day 5/6, selecting utilizable blastocysts for transfer/vitrification. To evaluate the performance of iDAScore to predict development into utilizable blastocysts, sensitivity, specificity, and area under ROC curve (AUC) values were calculated. Main results and the role of chance The blastocyst utilization rate was 43.8% (3990 utilizable blastocysts of 9111 day 2/3 embryos developing from 2PN zygotes). Prediction of utilizable blastocysts obtained AUCs of 0.768 (0.759 - 0.778) and 0.782 (0.773 - 0.791) for day 2 and day 3, respectively. These results suggest IDAScore prediction performed slightly better when calculated on day 3 than on day 2. The ability to discriminate between utilizable and non-utilizable blastocysts at different thresholds of iDAScore on day 2 and on day 3, suggests that embryos should have a minimum iDAscore of 5 on day 2 to obtain a high specificity of 89%, and a threshold of 6 on day 3 to obtain a high specificity of 88%. Lower sensitivities were observed for these potential thresholds, 35% on day 2 and 41% on day 3. Limitations, reasons for caution This is a retrospective analysis where most cycles have at least five zygotes that supported subsequent blastocyst development, limiting relevance for patients with fewer zygotes. IDAScore is developed to predict implantation potential, not utilizable blastocyst, thus could be an underestimation of the potential performance of a model for utilization prediction. Wider implications of the findings The iDAScore v2.0 may provide valuable information for embryologists and be useful as a prognostic tool to select patients with high chance to obtain blastocysts based on day2/3 time-lapse images and thereby may achieve similar live birth rate per transfer with no need for extended culture. Trial registration number Not applicable

Preimplantation genetic testing for aneuploidy helps to achieve a live birth with fewer transfer cycles for the blastocyst FET patients with unexplained recurrent implantation failure.

This retrospective cohort study aimed to investigate the value of preimplantation genetic testing for aneuploidy (PGT-A) as a screening test for patients suffering from unexplained recurrent implantation failure (RIF). After screening patients in one reproductive medicine center, twenty-nine, forty-nine and thirty-eight women (< 40years old) who had suffered unexplained RIF with PGT-A, or RIF without PGT-A, or no RIF with PGT-A were included. The clinical pregnancy rate and live birth rate per transfer, the conservative and optimal cumulative clinical pregnancy rates (CCPR) and live birth rates (CLBR) after three blastocyst FETs were analyzed. The live birth rate per transfer was significantly higher in the RIF + PGT-A group than that in the RIF + NO PGT-A group (47.6% vs. 24.6%, p = 0.014). After 3 cycles of FET, RIF + PGT-A group had significantly higher conservative CLBR and optimal CLBR compared to the RIF + NO PGT-A group (69.0% vs. 32.7%, p = 0.002 and 73.7% vs. 57.5%, p = 0.016), but had similar conservative and optimal CLBRs compared to the NO RIF + PGT-A group. The number of FET cycles required when half women achieved a live birth was 1 in the PGT-A group and 3 in RIF + NO PGT-A group. The miscarriage rates werenot different between the RIF + PGT-A and RIF + NO PGT-A, RIF + PGT-A and NO RIF + PGT-A groups. PGT-A did be superior in reducing the number of transfer cycles required to achieve a similar live birth rate. Further studies to identify the RIF patients who would benefit most from PGT-A are necessary.

Influence of ovarian reserves on assisted reproductive and perinatal outcomes in patients with endometriosis: a retrospective study.

To investigate the association between different ovarian reserves and reproductive and adverse perinatal outcomes in patients with endometriosis. Retrospective study. Reproductive Medicine Center in a hospital. Patients surgically diagnosed with endometriosis were divided into three groups according to their ovarian reserve: diminished ovarian reserve (DOR) group (n=66), normal ovarian reserve (NOR) group (n=160), and high ovarian reserve (HOR) group (n=141). None. Live birth rate (LBR), cumulative live birth rate (CLBR), and adverse perinatal outcome for singleton live births. There were significantly higher live birth and cumulative live birth rates in endometriosis patients with NOR or HOR than in those with DOR. For adverse perinatal outcomes, patients with NOR or HOR had no significant association with preterm birth, gestational hypertension, placenta previa, fetal malformation, abruptio placentae, macrosomia, or low birth weight, except for a decreased risk of gestational diabetes mellitus. Our study revealed that although patients with endometriosis with NOR and HOR had increased reproductive outcomes, patients with endometriosis with DOR had still an acceptable live birth rate and a similar cumulative live birth rate with available oocytes. Moreover, patients with NOR and HOR might not exhibit a decreased risk of abnormal perinatal outcomes, except for gestational diabetes mellitus. Multicenter prospective studies are needed to further clarify the relationship.

Ovulatory-cycle frozen embryo transfer: spontaneous or triggered ovulation and the impact of LH elevation at hCG triggering

The effect of the luteinizing hormone (LH) elevation before the human chorionic gonadotropin (hCG) trigger in ovulatory frozen-thawed embryo transfer (Ovu-FET) cycles has not been determined. We aimed to investigate whether triggering ovulation in Ovu-FET cycles affects the live birth rate (LBR), and the contribution of elevated LH at the time of hCG trigger. This retrospective study included Ovu-FET cycles performed in our center from August 2016 to April 2021. Modified Ovu-FET (hCG trigger) and true Ovu-FET (without hCG trigger) were compared. The modified group was divided according to whether hCG was administered, before or after LH increased to > 15 IU/L and was twice the baseline value. The modified (n = 100) and true (n = 246) Ovu-FET groups and both subgroups of the modified Ovu-FET, those who were triggered before (n = 67) or after (n = 33) LH elevation, had comparable characteristics at baseline. Comparison of true vs. modified Ovu-FET outcomes revealed similar LBR (35.4% vs. 32.0%; P = 0.62), respectively. LBR were similar between the modified Ovu-FET subgroups regardless of the hCG trigger timing (31.3% before vs. 33.3% after LH elevation; P = 0.84). In conclusion, LBR of Ovu-FET were not affected by hCG trigger or whether LH was elevated at the time of hCG trigger. These results add reassurance regarding hCG triggering even after LH elevation.

The live birth rate of vitrified oocyte accumulation for managing diminished ovarian reserve: a retrospective cohort study

BackgroundVitrified M-II oocyte accumulation for later simultaneous insemination has been used for managing POR. Our study aimed to determine whether vitrified oocyte accumulation strategy improves live birth rate (LBR) for managing diminished ovarian reserve (DOR).MethodsA retrospective study included 440 women with DOR fulfilling Poseidon classification groups 3 and 4, defined as the presence of serum anti-Müllerian hormone (AMH) hormone level < 1.2 ng/ml or antral follicle count (AFC) < 5, from January 1, 2014, to December 31, 2019, in a single department. Patients underwent accumulation of vitrified oocytes (DOR-Accu) and embryo transfer (ET) or controlled ovarian stimulation (COS) using fresh oocytes (DOR-fresh) and ET. Primary outcomes were LBR per ET and cumulative LBR (CLBR) per intention to treat (ITT). Secondary outcomes were clinical pregnancy rate (CPR) and miscarriage rate (MR).ResultsTwo hundred eleven patients underwent simultaneous insemination of vitrified oocyte accumulation and ET in the DOR-Accu group (maternal age: 39.29 ± 4.23 y, AMH: 0.54 ± 0.35 ng/ml), and 229 patients underwent COS and ET in the DOR-fresh group (maternal age: 38.07 ± 3.77 y, AMH: 0.72 ± 0.32 ng/ml). CPR in the DOR-Accu group was similar in the DOR-fresh group (27.5% vs. 31.0%, p = 0.418). However, MR was statistically higher (41.4% vs. 14.1%, p = 0.001), while LBR per ET was statistically lower (15.2% vs. 26.2%, p < 0.001) in the DOR-Accu group. There is no difference in CLBR per ITT between groups (20.4% vs. 27.5%, p = 0.081). The secondary analysis categorized clinical outcomes into four groups regarding patients’ age. CPR, LBR per ET, and CLBR did not improve in the DOR-Accu group. In the group of 31 patients, accumulated vitrified metaphase II (M-II) oocytes reached a total number of ≥ 15, and CPR improved among the DOR-Accu group (48.4% vs. 31.0%, p = 0.054); however, higher MR (40.0% vs. 14.1%, p = 0.03) resulted in similar LBR per ET (29.0% vs. 26.2%, p = 0.738).ConclusionsVitrified oocyte accumulation for managing DOR did not improve LBR. Higher MR resulted in lower LBR in the DOR-Accu group. Therefore, the vitrified oocyte accumulation strategy for managing DOR is not clinically practical.Trial registrationThe study protocol was retrospectively registered and was approved by Institutional Review Board of Mackay Memorial Hospital (21MMHIS219e) on August 26, 2021.

Pregnancy and neonatal outcomes of letrozole versus natural cycle frozen embryo transfer of autologous euploid blastocyst.

To investigate the pregnancy and neonatal outcomes of letrozole-stimulated frozen embryo transfer (LTZ-FET) cycles compared with natural FET cycles (NC-FET). Our retrospective cohort included all LTZ-FET (n = 161) and NC-FET (n = 575) cycles that transferred a single euploid autologous blastocyst from 2016 to 2020 at Stanford Fertility Center. The LTZ-FET protocol entailed 5mg of daily letrozole for 5days starting on cycle day 2 or 3. Outcomes were compared using absolute standardized differences (ASD), in which a larger ASD signifies a larger difference. Multivariable regression models adjusted for confounders: maternal age, BMI, nulliparity, embryo grade, race, infertility diagnosis, and endometrial thickness. The demographic and clinical characteristics were overall similar. A greater proportion of the letrozole cohort was multiparous, transferred high-graded embryos, and had ovulatory dysfunction. The cohorts had similar pregnancy rates (67.1% LTZ vs 62.1% NC; aOR 1.31, P = 0.21) and live birth rates (60.9% LTZ vs 58.6% NC; aOR 1.17, P = 0.46). LTZ-FET neonates on average were born 5.7days earlier (P < 0.001) and had higher prevalence of prematurity (18.6% vs. 8.0%NC, ASD = 0.32) and low birth weight (10.4% vs. 5.0%, ASD = 0.20). Both cohorts' median gestational ages (38weeks and 1day for LTZ; 39weeks and 0day for NC) were full term. There were similar rates of pregnancy and live birth between LTZ-FET and NC-FET cycles. However, there was a higher prevalence of prematurity and low birth weight among LTZ-FET neonates. Reassuringly, the median gestational age in both cohorts was full term, and while the difference in gestational length of almost 6days does not appear to be clinically significant, this warrants larger studies.

The effects of unexpected follicular growth and ovulation in artificial cycles: a retrospective cohort study of frozen, single-blastocyst transfer

To study the effects of unexpected follicular development and ovulation in artificial cycles (ACs) on pregnancy outcomes. A retrospective cohort study. A university-affiliated fertility center. A total of 1,427 patients who underwent a single, frozen-thawed blastocyst transfer with AC regimens from January 2014 to December 2020 at a university-affiliated fertility center were included. Unexpected follicular development and ovulation in ACs. Live birth rate (LBR), biochemical pregnancy rate, clinical pregnancy rate, and ongoing pregnancy rate. A total of 161 patients with unexpected follicular development and ovulation in ACs (ovulation group) and 1,266 patients without growing follicles in ACs (control group) were enrolled. The patients in the ovulation group were older and had higher levels of serum follicle-stimulating hormone and lower levels of serum antimüllerian hormone. After propensity score matching, the baseline characteristics between the 2 groups were comparable and no significant difference was observed in the LBR (ovulation group, 39.0% vs. control group, 39.0%), biochemical pregnancy rate (ovulation group, 60.3% vs. control group, 58.2%), clinical pregnancy rate (ovulation group, 53.4% vs. control group, 50.7%), or ongoing pregnancy rate (ovulation group, 42.5% vs. control group, 40.4%). Moreover, the patients in the ovulation group showed a lower risk of hypertensive disorders of pregnancy (HDP) (1.6% vs. 15.3%). A subgroup analysis of women who delivered singleton live-born babies also demonstrated that unexpected follicular development and ovulation in ACs was associated with a decreased risk of HDP (adjusted odds ratio, 0.070; 95% confidence interval, 0.007-0.712) and an increased risk of large-for-gestational-age infants (adjusted odds ratio, 4.046; 95% confidence interval, 1.319-12.414). Women with unexpected follicular development and ovulation during single frozen-thawed blastocyst transfer with AC regimens had a similar LBR and a reduced risk of HDP compared with those with routine AC regimens, and singleton neonates had an increased risk of being large for gestational age.

The Effect of Short-Term Aspirin Administration during Programmed Frozen-Thawed Embryo Transfer on Pregnancy Outcomes and Complications.

Low-dose aspirin is widely used during frozen-embryo transfer (FET) cycles. Its anti-platelet property makes it a potentially useful drug for the prevention of hypertension disorders of pregnancy (HDP). However, the existing evidence about the effect of short-term aspirin administration on pregnancy outcomes is not clear. In our study, we retrospectively investigated women who had their first or second FET cycles at the Reproductive Hospital Affiliated with Shandong University from April 2017 to December 2020. A total of 4454 programmed FET cycles were recruited. According to whether aspirin was administrated in the protocols, the patients were divided into two groups: The Control group (n = 2793, 85 of them using donor sperm) and the Aspirin group (n = 1661, 35 of them using donor sperm). We analyzed the pregnancy outcomes and pregnancy complications of these cycles and observed similar live birth rates. We found that the short-term use of aspirin at a dosage of 50 mg per day for women undergoing programmed FET did not elevate the live birth rate or decrease the incidence of a series of pregnancy complications, including HDP. Based on our experience, short-term administration of low-dose aspirin may not improve the outcomes of young women undergoing frozen-thawed embryo transfer cycles.

Transfer of the fittest: using preimplantation genetic testing for aneuploidy to select embryo(s) most likely to lead to live birth

Preimplantation genetic testing for aneuploidy (PGT-A) was developed to identify euploid embryos from a cohort of embryos with unknown ploidy produced during an invitro fertilization (IVF) cycle. In recent years, the ability of PGT-A to improve IVF outcomes has come into question. The goal of this review was to summarize the major randomized controlled trials (RCTs) and nonselection studies evaluating the benefit of PGT-A to improve the live birth rates (LBRs). We argue that the LBR per transfer is more relevant to the individual patient than the cumulative LBR as a means to minimize the burden of IVF by reducing futile transfers, pregnancy losses, and ongoing aneuploidy. The early RCTs demonstrate improved implantation rates and LBRs with PGT-A for embryo selection vs. traditional morphology. However, these studies are limited by the small sample size and a bias toward good-prognosis patients. Further studies using next-generation sequencing found more variable results but did confirm an improvement in the LBRs per transfer in an older population with a higher baseline risk of aneuploidy. The largest RCT to date showed similar cumulative LBRs in the PGT-A and control groups after biopsy and sequential transfer of up to 3 blastocysts with a significant reduction in the cumulative clinical pregnancy loss rate in the PGT-A group. Nonselection studies evaluating pregnancy outcomes after transfer of euploid vs. aneuploid embryos demonstrate near-perfect negative predictive value for an aneuploid result to predict live birth. Putative mosaic embryos had similar LBRs compared with euploid embryos. The available RCTs and nonselection studies support the practice of using PGT-A to identify euploid embryos for transfer, especially in an older population, while simultaneously selecting against aneuploid embryos, without negative impact on the total reproductive potential of the cycle.

The developmental competence of human metaphase I oocytes with delayed maturation in vitro

To evaluate whether metaphase I (MI) oocytes completing maturation invitro to metaphase II ("MI-MII oocytes") have similar developmental competence as the sibling metaphase II (MII) oocytes that reached maturity invivo. Retrospective cohort study. Academic medical center. A total of 1,124 intracytoplasmic sperm injection (ICSI) cycles from 800 patients at a single academic center between April 2016 and December 2020 with at least 1 MII oocyte immediately after retrieval and at least 1 sibling "MI-MII oocyte" that was retrieved as MI and matured to MII in culture before ICSI were included in the study. None. A total of 7,865 MII and 2,369 sibling MI-MII oocytes retrieved from the same individuals were compared for the fertilization and blastocyst formation rates. For patients who underwent single euploid blastocyst transfers (n = 406), the clinical pregnancy, spontaneous pregnancy loss, and live birth rates were compared between the 2 groups. The fertilization rate was significantly higher in MII oocytes than in delayed matured MI-MII oocytes (75.9% vs. 56.1%). Similarly, the blastocyst formation rate was higher in embryos derived from MII oocytes than in those from MI-MII oocytes (53.8% vs. 23.9%). The percentage of euploid embryos derived from MII oocytes was significantly higher than that of those from MI-MII oocytes (49.2% vs. 34.7%). Paired comparison of sibling oocytes within the same cycle showed higher developmental competence of the MII oocytes than that of MI-MII oocytes. However, the pregnancy, spontaneous pregnancy loss, and live birth rates after a single euploid blastocyst transfer showed no statistically significant difference between the 2 groups (MII vs. MI-MII group, 65.7% vs. 74.1%, 6.4% vs. 5.0%, and 61.5% vs. 70.0%, respectively). Compared with oocytes that matured invivo and were retrieved as MII, the oocytes that were retrieved as MI and matured to MII invitro before ICSI showed lower developmental competence, including lower fertilization, blastocyst formation, and euploidy rates. However, euploid blastocysts from either cohort resulted in similar live birth rates, indicating that the MI oocytes with delayed maturation can still be useful even though the overall developmental competence was lower than that of their invivo matured counterparts.

Preimplantation genetic testing for aneuploidy in patients with low embryo numbers: benefit or harm?

We sought to explore the utility of preimplantation genetic testing for aneuploidy (PGT-A)in a poor prognosis group of womenwith few embryos available for transfer. This was a retrospective matched cohort study examining records for first or second-cycle IVF patients with 1 to 3 blastocysts. The study group comprised 130 patients who underwent PGT-A on all embryos. The control group included 130 patients matched by age, BMI, and blastocyst number and quality who did not undergo PGT-A during the same time period. The live birth rate (LBR) per embryo transfer (ET)were similar in the PGT-A and control groups, and the spontaneous abortion (SAB) rate was the same (23%). However, we found a significantly higher LBR per oocyte retrieval in the control group vs the PGT-A group (43% vs 20%, respectively) likely due to the many no-euploid cyclesin the PGT-A group. In a subgroup analysis for age, the similar LBR per ET persisted in women < 38. However, in older women, there was a trend to a higher LBR per ET in the PGT-A group (43%) vs the control group (22%) but a higher LBR per oocyte retrieval in the control group (31%) vs the PGT-A group (13%). Overall, we observed a significant increase in LBR per oocyte retrieval in women in the control group compared to women undergoing PGT-A, and no difference in SAB rate. Our data suggests that PGT-A has no benefit in a subpopulation of women with few embryos and may cause harm.

Effectiveness and Safety of Two Consecutive Cycles of Single Embryo Transfer Compared With One Cycle of Double Embryo Transfer: A Systematic Review and Meta-Analysis.

ObjectiveTo date, evidence regarding the effectiveness and safety of two consecutive cycles of single embryo transfer (2SETs) compared with one cycle of double embryo transfer (DET) has been inadequate, particularly considering infertile women with different prognostic factors. This study aimed to comprehensively summarize the evidence by comparing 2SETs with DET.MethodsPubMed, Embase, Cochrane Library databases, ClinicalTrails.gov, and the WHO International Clinical Trials Registry Platform were searched up to March 22, 2022. Peer-reviewed, English-language randomized controlled trials (RCTs) and observational studies (OS) comparing the outcomes of 2SETs with DET in infertile women with their own oocytes and embryos were included. Two authors independently conducted study selection, data extraction, and bias assessment. The Mantel–Haenszel random-effects model was used for pooling RCTs, and a Bayesian design-adjusted model was conducted to synthesize the results from both RCTs and OS.Main ResultsTwelve studies were finally included. Compared with the DET, 2SETs were associated with a similar cumulative live birth rate (LBR; 48.24% vs. 48.91%; OR, 0.97; 95% credible interval (CrI), 0.89–1.13, τ2 = 0.1796; four RCTs and six observational studies; 197,968 women) and a notable lower cumulative multiple birth rate (MBR; 0.87% vs. 17.72%; OR, 0.05; 95% CrI, 0.02–0.10, τ2 = 0.1036; four RCTs and five observational studies; 197,804 women). Subgroup analyses revealed a significant increase in cumulative LBR (OR, 1.33; 95% CrI, 1.29–1.38, τ2 = 0) after two consecutive cycles of single blastocyst transfer compared with one cycle of double blastocyst transfer. Moreover, a lower risk of cesarean section, antepartum hemorrhage, preterm birth, low birth weight, and neonatal intensive care unit admission but a higher gestational age at birth and birth weight were found in the 2SETs group.ConclusionCompared to the DET strategy, 2SETs result in a similar LBR while simultaneously reducing the MBR and improving maternal and neonatal adverse outcomes. The 2SETs strategy appears to be especially beneficial for women aged ≤35 years and for blastocyst transfers.

P-102 Progesterone luteal-phase support during IUI cycle should be added depending on women age and/or on previous mid-luteal progesterone assessment to promote live births

Abstract Study question To determine the Mid-luteal progesterone (MLP) threshold which could condition live-birth (LB) after IUI, and effects of additional progesterone luteal-phase support (LPS) in subsequent cycles. Summary answer MLP threshold is age-dependant. LPS should only be used if previous MLP is below the age related threshold, as its inappropriate use reduces LB rate. What is known already Progesterone is essential to prepare and maintain the uterus suitable for a possible pregnancy. During IUI, it is not clear if LPS is beneficial to obtain a live birth, and whether it should be introduced systematically or only in women with a low MLP assessment during a previous cycle. Study design, size, duration In an audit purpose, we performed a retrospective uni-centric analysis of 705 IUl cycles performed from January 2015 to March 2020 in couples which fertility work-up concluded to unexplained infertility, mild male infertility or PCOS with no pregnancy after 3 cycles of clomiphene citrate. Our primary outcome was LB. Participants/materials, setting, methods IUI was performed after ovarian stimulation with gonadotrophins. MLP was assessed using immuno assay method, days 7 post-IUI. LPS (Cyclogest® 200 mg/day) was added when consultant considered former cycle’s MLP was too low. MLP thresholds were defined without LPS using a ROC Curve, considering subgroups of patient’s age. LB rate was analyzed using Multivariate Gill Andersen models to take into account repetitions of IUI cycles. Prognostic factors for LBR were investigated using a Cox model. Main results and the role of chance Women were 33.6±3.9 years old. We obtained 99 (14%) LB. In women who didn’t receive LPS, regardless of their age, MLP threshold was 57.5 nmo/l (AUC=0.57). Multivariate logistic regression modeling identified MLP assessment as a significant prognostic factor for obtaining LB after IUI (OR = 1.668, CI95%[1.023; 2.721], p = 0.0402). When also considering women’s age, a cut-off of 36 years old was computed which allowed more fitted age-related MLP thresholds for obtaining LB after IUI. In women &amp;lt;36 years old, MLP threshold was 39.5 nmol/l (AUC=0.57) whereas it was 60.5 nmol/L (AUC=0.57) for age ≥36. Age-related thresholds were more predictive of LB than initial age independent threshold according to Akaike Criteria (1168.48 versus 1198.96, respectively). Using the whole population (i.e. receiving or not LPS), the multivariate analysis highlighted that, compared to women with MLP above their age related threshold who (appropriately) didn’t receive LPS: - Women below their age-related MLP threshold who appropriately receive LPS had similar LB rate: OR = 0.5474, CI95%[0.1857-1.6138], p = 0.2747. - Women below their age-related MLP threshold who didn’t receive LPS (inappropriately) had a significantly lower LB rate: OR = 0.4794, CI95%[0.2727-0.8427], p = 0.0106. - Women above their age-related MLP threshold who received LPS (inappropriately) had a significantly lower LB rate: OR = 0.5627, CI95%[0.3302-09587], p = 0.0433. Limitations, reasons for caution Because of the retrospective design of our study and because of the limited number of included couples, our results should be considered with caution. Confirmation is needed with further prospective studies with a larger number of participants. Wider implications of the findings Our study highlight for the first time the impact of age on the LPS strategy after IUI, and emphases the need for personalized fertility medicine based on previous MLP assessment when considering LPS. Trial registration number No needed, NHS Audit

P-678 Does gonadotropin dose adjustment in inadequate ovarian response during controlled ovarian hyperstimulation improve the live birth rates of patients with diminished ovarian reserve?

Abstract Study question Does gonadotropin dose adjustment in inadequate ovarian response during controlled ovarian hyperstimulation improve the live birth rates of patients with diminished ovarian reserve? Summary answer The increasing dose adjustment of the gonadotropin according to the ovarian response during COH in DOR provides similar live birth rates to the fixed-dose group. What is known already Since the poor ovarian response is associated with low pregnancy rates and high cycle cancellation rates, the ovarian response should be predicted, especially for stimulation protocol and gonadotropin dose adjustment before COH is initiated. On the other hand, the predicted gonadotropin dose may not be enough for the ovarian response, and the dose adjustment may be required. Nevertheless, the literature has conflicting results on whether dose adjustment during COH improves the pregnancy results. Study design, size, duration This retrospective cohort study was conducted at a tertiary university hospital's ART (assisted reproductive technologies) center. The electronic database of the ART center was screened between the years 2012-2021, and the DOR patients who underwent ICSI-ET (intra-cytoplasmic sperm injection – embryo transfer) were selected. Bologna criteria were used to determine the diminished ovarian reserve. Patients were divided into two groups depending on the presence of dose adjustment on the first ultrasound control during COH. Participants/materials, setting, methods Women who underwent single–fresh good quality (Gardner A or B) blastocyst transfer and aged between 18-40 years, without male infertility and endometrial pathology were included in, and after exclusion, 498 patients were enrolled in the study. Flexible antagonist protocol was used for COH. A vaginal micronized progesterone capsule (3x200 mg) was prescribed for luteal phase support after oocyte retrieval. Live birth rate was determined as the singleton live birth after the 24th week of pregnancy. Main results and the role of chance There were 188 patients in the dose adjustment (DA) group and 310 patients in the fixed-dose (FD) group. The demographic parameters were similar between the groups (Age, Body Mass Index, Ovarian Reserve Parameters). The mean women age was 33.8+4 in the DA group and 33.6+4.1 in the FD group (p = 0.6). The started gonadotropin dose was similar in both groups (300 IU). The type of gonadotropin was mostly HMG in the DA group (67% in DA vs. 48% in the FD group, p = 0.01). The median dose adjustment on the first control was +75 IU in the DA group, and as expected, the total gonadotropin consumption was significantly higher in the DA group (Median values; 3900 vs. 3000 IU, p &amp;lt; 0.01). The follicle output rates, follicle to oocyte indexes, and the embryology parameters were comparable between the groups (number of picked up oocytes, metaphase-2 oocytes, and 2PN embryos). The positive pregnancy rate was 19.7% (36/188) in the DA group vs. 19.1% (61/310) in the FD Group (p = 0.4). The primary outcome of the study; live birth rates were 12% in the DA group vs. 9% in the FD group, and the results were statistically similar (p = 0.3). Limitations, reasons for caution Retrospective design and the sample size limit the power of the study. Wider implications of the findings Our study showed that the gonadotropin dose adjustment in inadequate ovarian response during COH provides similar live birth rates to the fixed-dose group. In patients with inadequate response, dose adjustment may be a necessary action. Trial registration number Not applicable

Planned oocyte cryopreservation for fertility preservation

Background: Oocyte cryopreservation opens up opportunities for women to preserve fertility when it is necessary to postpone pregnancy. After the advent of vitrification, the results of oocyte cryopreservation were significantly improved compared to conventional slow-freezing. Through these improvements, oocyte cryopreservation was introduced to overcome a decline in fecundity due to an increase in age, and this modality is defined as planned oocyte cryopreservation.Current Concepts: Oocytes cryopreserved through vitrification appear to result in similar clinical pregnancy rates and live birth rates compared to fresh oocytes, though the evidence is still limited. It has been reported that the live birth rate increases when the planned oocyte cryopreservation is performed at a younger age. Obstetrical and neonatal outcomes appear similar between vitrified and fresh oocytes.Discussion and Conclusion: Preliminary data supports planned oocyte cryopreservation as a feasible modality resulting in fertility preservation and subsequent live births. The fact that performing the procedure at a younger age can increase the oocyte yield, oocyte efficacy, and live birth rate can be discussed along with patient consultation. However, as there is still a lack of data on the standardized live birth rate, the number of oocytes to be collected, and the long-term effect on the children; more well-designed studies are needed to improve counseling and decision-making in patients seeking this treatment.