Significant Difference In Live Birth Rate Research Articles

P-579 Is the use of donated oocytes effective to reestablish live birth rates? Reproductive outcomes of 5313 euploid embryo transfers in autologous versus egg donation cycles

Abstract Study question Is live birth rate of autologous versus donor cycles similar after a euploid embryo transfer? Summary answer The live birth rate was significantly higher in autologous cycles after a euploid embryo transfer. What is known already Advanced maternal age (AMA) is a detrimental factor for patients to achieve a successful outcome in ART. Physiological ovarian aging negatively affects oocyte quality and quantity. Thus, the number of cycles with donated oocytes is increasing for AMA patients worldwide, with the perspective of surpass the oocyte factor and achieve a live birth in similar rates as younger patients. The goal of this study was to compare the live birth rates of autologous versus donor cycles after a euploid embryo transfer. Study design, size, duration Observational cohort study including all patients of IVF cycles with a euploid embryo transfer after PGT-A (NGS technology), according to medical referral between Jan/2016 and Dec/2020 (n = 3623 patients and 4025 cycles) in a private ART center. Participants/materials, setting, methods Reproductive outcomes between autologous and egg donation cycles were compared and data were analyzed in the follow subgroups: cycles with a fresh oocyte and fresh embryo transfer (FRESH), frozen embryo transfer (FET) and fresh embryo transfer from frozen oocytes (FOT). Positive pregnancy test (PPT), clinical pregnancy (CP), clinical miscarriage (CM) and live birth (LB) rates were compared. Kruskal-Wallis and Fisher test were applied for statistical analysis, significance was considered if p < 0,05. Main results and the role of chance In total, 3623 patients – 88.9% autologous and 11.1% with donated oocytes – were included. They performed 4025 ETs (3591/434) with 5313 biopsied blastocysts (4736/577) in a mean of 1,32/1,33 blastocysts per transfer in autologous/donated cycles respectively. The majority of patients using autologous and donated oocytes underwent a FET (97,2% and 63,1%), followed by FOT (1,5% and 34,7%) and FRESH (1,3% and 2,2%, respectively). Mean maternal age in autologous and donor cycles was 37,76±3,9yo and 43,47±4,26yo and oocyte donors were 24,99±3,86yo. In subgroups, autologous patients in FRESH were 38,33±2,69 yo, similar in FET (37,73±3,93 yo) and older in FOT, 39,25±3,93 yo (p = 0,03). Patients in donor cycles showed no difference in age. PPT and CP were similar in autologous and donated cycles (PPT: 59,2% vs 54,8%, p = 0.08; CP: 52,2% vs 48,2%, p = 0.11). In subgroup analysis, PPT and CP were higher in donated cycles vs autologous cycles for FOT (PPT: 50,7% vs 33,3%, p = 0.004; CP: 40,7% vs 20,8%, p = 0.01). Overall, CM were higher in donated cycles (15,5% vs 10,6%, p = 0.03), especially after FET (16,8% vs 10,6%, p = 0.025). LB rates were higher in autologous compared to donated cycles (37,8% vs 29,5%, p = 0.0007). There was no significant difference in LB rates in subgroup analysis. Limitations, reasons for caution This is a large cohort study; however, we cannot exclude potential bias due its retrospective nature. Including only euploid embryos, we excluded bias on ploidy status when comparing autologous versus donated oocytes cycles, yet the potential harmful of embryo biopsy may not be neglect. Wider implications of the findings Live birth rate was significantly higher in autologous cycles after a euploid embryo transfer, regardless of subgroups. AMA patients that choose to undergo an IVF treatment with donated oocytes should be aware that there are other important factors related to a successful reproductive outcome, including immunological adaptation and endometrial aging. Trial registration number Not applicable.

P-212 Balancing success and safety in assisted reproductive technologies cycles: the outcomes of transferring poor-quality blastocyst or day 5 slow-growing embryos with good-quality blastocyst

Abstract Study question Does transferring two mixed-quality embryos improve the live birth rate (LBR) without increasing the multiple gestation rate compared to the single good-quality blastocyst (GQB) transfers? Summary answer The transfers of single GQB and two mixed-quality embryos show similar LBRs, however, the multiple gestation rate was significantly higher in double embryo transfer groups. What is known already Due to higher LBR after blastocyst transfer, the single embryo transfer (SET) strategy has gained popularity worldwide. Despite that double-embryos transfers (DET) demonstrate higher LBR than SET, multiple gestation rates (MGRs) are higher in DET. To reduce MGR but still accomplish high LBR, DETs could be performed using embryos of mixed-quality. It has been suggested that the transfer of GQB with poor-quality blastocyst (PQB) could increase LBR without increasing MGR. Alternatively, when the embryo transfer is scheduled in a fresh cycle, the DET could be performed with GQB and day 5 slow-growing embryo (SGE) – early blastocyst or morula. Study design, size, duration This study included assisted reproductive technologies (ART) cycles with fresh embryo transfer on day 5, between 2015 and 2021, for patients under 34 years. Selected ART cycles were assigned into five groups: SET with GQB (SET-GQB, n = 754); DET with two GQBs (DET-GQB, n = 306); DET with one GQB and one PQB (DET-GP, n = 75); DET with one GQB and one day 5 SGE (DET-GS, n = 386), DET with two day 5 SGE (DET-SGE, n = 209). Participants/materials, setting, methods According to Gardner and Schoolcraft’s grading system, blastocyst morphological assessment was performed on day 5. Blastocysts graded as AA, AB, BA, and BB with a degree of expansion ≥3 were classified as GQBs, whereas blastocysts graded ВС, СВ, СС with a degree of expansion ≥3 were classified as PQBs. Day 5 morulas and blastocysts with degree of expansion 1 were classified as slow-growing embryos. The cycles with donor gametes, preimplantation genetic testing were excluded. Main results and the role of chance The LBR was significantly higher in DET-GQB than in SET-GQB [53,59% (164/306) vs 40,58% (306/754); P < 0,001]. There were no significant differences in implantation rate (IR) and miscarriage rate (MR) between SET-GQB and DET-GQB [47,88% (361/754) vs. 44,12% (270/612) P = 0,165], [12,19% (44/361) vs. 10,00% (27/270) P = 0,389]. However, the MGR was significantly higher in DET-GQB compared to SET-GQB [36,59% (60/164) vs 1,31% (4/306) P < 0,001]. When SET-GQB was compared with DET-GS, DET-GP there were no significant differences in LBR: [40,58% (306/754) vs. 39,64% (153/386) P = 0,757; vs. 41,33% (31/75) P = 0,899]. The IR was significantly higher in SET-GQB than in DET-GS and DET-GP [47,88% (361/754) vs. 30,70% (237/772) P < 0,001; vs. 30,00% (45/150) P < 0,001]. There were no significant differences in MR between SET-GQB and DET-GS, DET-GP [12,19% (44/361) vs. 17,30% (41/237) P = 0,079; vs. 11,11% (5/45) P = 0,834]. However, the MGR was significantly lower in SET-GQB compared to DET-GS, DET-GP [1,31% (4/306) vs. 18,95% (29/153) P < 0,001; vs. 22,58% (7/31) P < 0,001]. The IR and LBR were significantly higher in SET-GQB compared to DET-SGE [47,88% (361/754) vs 16,99% (71/418) P < 0,001], [40,58% (306/754)vs 19,14% (40/209) P < 0,001]. The MR and MGR were significantly lower in SET-GQB than in DET-SGE [12,19% (44/361) vs 32,39% (23/71) P < 0,001], [1,31% (4/306) vs 15,00% (6/40) P < 0,001]. Limitations, reasons for caution The study is limited due to the uneven distribution and a low number of participants in group DET-GP. Blastocyst morphological assessment remains subjected to a human factor. It was impossible to form a group where two PQBs were transferred, as there were only a few cases of such transfers. Wider implications of the findings Transferring an additional poor-quality embryo (poor-quality blastocyst or day 5 slow-growing embryo) does not increase the live birth rates. However, it significantly raises the multiple gestation rate. Despite the low live birth rate when two day 5 slow-growing embryos are transferred, the multiple gestation rate significantly increases, compared to SET. Trial registration number Not applicable

Different doses of recombinant FSH and determining parameters of oxidative stress.

This study aimed to examine if there is a connection between recombinant FSH dose and OS parameters in serum and the impact on IVF outcome. This study consisted of 101 participants that went through IVF procedures. Parameter that were tested are SOD, SH groups and MDA. Serum samples were drawn before stimulation and on the last day of ovarian stimulation. Two groups were formed according to the dose of gonadotropins (rFSH). In both groups there were no significant differences in live-birth rate and miscarriage. In both groups mean serum MDA and SH-groups were significantly higher after ovarian stimulation, but mean serum SOD was significantly lower when compared to values before stimulation. There were less patients without OS before stimulation. Our results suggest that there is a difference in serum concentration in groups SOD, SH groups and MDA at the beginning and at the end ovarian stimulation. On the other hand, dose of rFSH is not related with change of parameters for oxidative stress, quality of oocytes, embryos, fertilization, pregnancies, and miscarriage rate. Patients without oxidative stress before the IVF procedure needed lower doses of gonadotropins during stimulation.

Ultra-low-dose and very-low-dose Lupron downregulation protocols for poor responders based on POSEIDON group 3 and 4 classifications.

The objective of this study was to assess if very-low-dose Lupron (VLDL) and ultra-low-dose Lupron (ULDL) protocols can have comparable cycle outcomes when compared to other "poor responder" stimulation protocols based on POSEIDON classification groups 3 (PG3) and 4 (PG4). A retrospective cohort study at a single, large academic center was performed. Women in PG3 (age < 35, AMH < 1.2ng/mL) or PG4 (age ≥ 35, AMH < 1.2ng/mL) undergoing in vitro fertilization using an ULDL (Lupron 0.1 to 0.05mg daily), VLDL (Lupron 0.2 to 0.1mg daily), microflare (Lupron 0.05mg twice a day), estradiol priming/antagonist, antagonist, or minimal stimulation protocols from 2012 to 2021 were included. The primary outcome was the number of mature oocytes (MII) obtained. The secondary outcome was live birth rate (LBR). The cohort included 3601 cycles. The mean age was 38.1 ± 3.8years. In the PG3 group, ULDL and VLDL protocols produced a comparable number of MIIs (5.8 ± 4.3 and 5.9 ± 5.4, respectively) and live births (33.3% and 33.3%, respectively) when compared to other protocols. In the PG4 group, ULDL and VLDL protocols resulted in a higher percentage of MIIs when compared to microflare or minimal stimulation (Microflare/ULDL: adjusted relative risk (aRR) 0.78 (95% CI 0.65, 0.95); min stim/ULDL: aRR 0.47 (95% CI 0.38, 0.58); microflare/VLDL: aRR 0.77 (95% CI 0.63, 0.95); min stim/VLDL: aRR 0.47 (95% CI 0.38, 0.95)). There were no significant differences in LBR. Dilute Lupron downregulation protocols have comparable outcomes to other poor responder protocols and are reasonable to use.

Elevated body mass index in modified natural cycle frozen euploidembryo transfers is not associated with live birth rate.

To assess the impact of elevated BMI on the success of modified natural cycle frozen embryo transfers (mNC-FET) of euploid embryos. This retrospective cohort study at a single academic institution reviewed mNC-FET involving single euploid blastocysts from 2016 to 2020. Comparison groups were divided by pre-pregnancy BMI (kg/m2) category: normal weight (18.5-24.9), overweight (25-29.9) or obese (≥ 30). Underweight BMI (< 18.5) was excluded from the analysis. The primary outcome was live birth rate (LBR) and secondary outcome was clinical pregnancy rate (CPR), defined as presence of fetal cardiac activity on ultrasound. Absolute standardized differences (ASD) were calculated to compare descriptive variables and p-values and multivariable logistic regressions with generalized estimating equations (GEE) were used to compare pregnancy outcomes. 562 mNC-FET cycles were completed in 425 patients over the study period. Overall, there were 316 transfers performed in normal weight patients, 165 in overweight patients, and 81 in obese weight patients. There was no statistically significant difference in LBR across all BMI categories (55.4% normal weight, 61.2% overweight, and 64.2% obese). There was also no difference for the secondary outcome, CPR, across all categories (58.5%, 65.5%, and 66.7%, respectively). This was confirmed in GEE analysis when adjusting for confounders. While increased weight has commonly been implicated in poor pregnancy outcomes, the effect of BMI on the success of mNC-FET remains debated. Across five years of data from a single institution using euploid embryos in mNC-FET cycles, elevated BMI was not associated with reduced LBR or CPR.

Blastocyst Transplantation Strategies in Women of Different Ages

(1) Background: Single blastocyst transfers (SBT) and double blastocyst transfers (DBT) are widely used in clinical practice. The objective of this study was to investigate the application of these two strategies in women of different ages. (2) Methods: Analysis was carried out on 5477 frozen embryo transfer cycles of women in different ages. All the cycles were divided into three groups according to the age of the included women: <35, 35-39, and >39. The live birth rate (LBR) and multiple birth rate (MBR) between the SBT and DBT among these groups, respectively, were compared. (3) Results: In the women < 35 group, the LBR was similar in SBT and DBT, but the MBR was higher in DBT than SBT. In women 35-39, with >10 oocytes retrieved, the MBR in DBT was significantly higher than SBT, but there was no significant difference in LBR between the two groups; with ≤10 oocytes retrieved, the LBR in DBT were significantly higher than SBT, but the MBT was not significantly different between the two groups. In women > 39, the LBR and MBR were lower in the SBT than DBT, but the differences were not statistically significant. (4) Conclusions: Selective SET is appropriate for most young women, whereas older women are advised to make individualized choices based on the number of oocytes retrieved and blastocyst quality.

Impact of the duration of oestradiol treatment on live birth rate in Hormonal Replacement Therapy cycle before frozen blastocyst transfer

Although the duration of progesterone administration in Hormonal Replacement Therapy (HRT) cycles before frozen embryo transfer is standardized, the optimal duration of oestrogen treatment remains controversial. In this monocentric retrospective study conducted in all single frozen blastocyst transfer (FBT) performed with HRT between January 2016 and July 2019, we evaluated the association between the duration of oestradiol treatment before FBT and live birth rate (LBR) in HRT cycles. Cycles were gathered in 3 groups according to quartiles of duration of oestrogen treatment. LBR was compared across the 3 groups and multivariate analysis was performed. We included 2235 single FBT cycles; 507, 1257 and 471 with E2 treatment below 23 days, 23–30 days (reference) and more than 30 days respectively. After multivariate analysis and adjustment, no significant difference in LBR was found between below 23 or more than 30 days and reference groups (OR = 0.93 [0.68–1.27] and OR = 1.29 [0.88–1.89] respectively). Complementary sensitivity analysis led to a non-significant adjusted OR = 1.66 [IC 0.9–3.1]. In conclusion, our study showed that the duration of E2 treatment in HRT cycles before FBT is not associated with LBR.

Day of trophectoderm biopsy and embryo quality are associated with outcomes following euploid embryo transfer.

To compare clinical outcomes following transfer of euploid blastocysts of varying quality biopsied on day 5 versus day 6. Retrospective cohort study to evaluate embryo transfer outcomes for women undergoing autologous cryopreserved next generation sequencing euploid single embryo transfer from 10/2015 to 2/2022 at an academic IVF program. The primary outcome was live birth rate (LBR). Secondary outcomes included ongoing pregnancy rate (OPR), implantation rate (IR), and miscarriage rate (SAB rate). Five hundred and fifty-five transfers from 418 patients were analyzed. Euploid embryos biopsied on day 5 resulted in higher LBR compared to those biopsied on day 6 (62.3% vs. 49.6%; aRR 0.81 95% CI 0.65-0.996). When stratified by biopsy day and blastocyst quality, there was no difference in IR, OPR, and SAB rate for good, fair, and poor quality blastocysts biopsied on day 5 versus day 6. However, day 5 good quality embryos were associated with a higher LBR compared to day 6 good quality embryos (74.3% vs. 51.3%; aRR 0.69; 95% CI 0.48-0.999). There were no significant differences in LBR for fair and poor quality embryos biopsied on day 5 versus day 6. Overall LBR are higher for euploid embryos biopsied on day 5 versus day 6. When stratified by embryo quality and day of biopsy, LBR are significantly higher for good quality day 5 versus day 6 embryos. When choosing between multiple euploid embryos, day 5 biopsied good quality embryos should be preferentially selected for transfer over day 6 embryos of the same quality.

A Cross-Sectional Analysis of Live Birth Rates in Day 5 Fresh Versus Vitrified Single Blastocyst Transfer Cycles

Background: The use of frozen embryo transfers (FETs) in assisted reproduction has increased worldwide. Proponents of FETs suggest that controlled ovarian hyperstimulation (COH) in a fresh transfer impairs endometrial-embryo synchronicity, however there has been conflicting evidence on live birth rate (LBR) and clinical pregnancy rate (CPR) outcomes. Aim: To compare LBRs and CPRs between single autologous day 5 fresh versus vitrified blastocyst transfer cycles, in order to investigate the impact of COH on embryo-endometrium asynchrony. Method: A large cross-sectional analysis of 6,002 embryo transfers (ETs), comprising of 3774 fresh and 2228 FET cycles from 2016-2019. Inclusion criteria: first two stimulation cycles, single ET, and no pre-implantation genetic testing for aneuploidy (PGT-A). Multivariate analysis performed, also sub-group analysis for high-responders (&gt;20 oocytes collected). Results: Univariate analysis showed no absolute difference in LBR (28.3% vs 27.4%, p=0.43) and CPR (32.2% vs 30.9%, p=0.30), however multivariate analysis demonstrated significantly lower LBR (OR 0.864, p&lt;0.05, 95% CI 0.749-0.997) and CPR (OR 0.852, p&lt;0.05, 95% CI 0.742-0.979) in FET compared to fresh ETs. Younger patient age, previous IVF pregnancy, advanced blastocyst expansion, higher trophectoderm quality and lower cumulative number of ETs all improved the odds of both LBR and CPR (p&lt;0.001). Conventional IVF, rather than ICSI, improved CPR (p&lt;0.05) but not LBR (p=0.138). BMI affected neither LBR (p=0.492) nor CPR (p=0.359). In sub-group multivariate analysis of high-responders, no significant difference in LBR (p=0.439) or CPR (p=0.450) noted. Conclusion: This study demonstrates a relative higher LBR and CPR for fresh ETs compared to FETs, in multivariate analysis. Having a FET decreased the odds of LBR by nearly 14% compared to fresh ET, when adjusted for confounders. Our results suggest that universal freeze-all strategy, without appropriate indication, may lead to suboptimal outcomes. In high-responders, freeze-all cycles may be beneficial, as adjusted outcomes appear to be similar.

P-361 Granulocyte colony-stimulating factor and platelet-rich plasma improve pregnancy outcomes in patients with thin endometrium and recurrent implantation failure (RIF) in frozen embryo transfer cycles (FET)

Abstract Study question Does the use of granulocyte colony-stimulating factor (G-CSF) and platelet-rich (PRP) plasma improve endometrial thickness and pregnancy outcome in patients with thin endometrium and RIF? Summary answer The use of G-CSF and PRP improve the endometrial thickness and pregnancy outcome in patients with thin endometrium and RIF undergoing artificial FET cycles What is known already Thin endometrium is a negative prognostic factor for achieving pregnancy, which occurs in 2.4% of assisted reproductive technology cycles. According to previous studies use of G-CSF and PRP are perspective methods for these patients’ management. G-CSF is a polypeptide that belongs to the colony-stimulating factor glycoprotein group. PRP is derived from patient’s own blood and contains platelets’ growth factors that promote reparation in tissues. However, there is limited data about IVF treatment success after G-CSF or PRP perfusion in patients with thin endometrium and RIF, also there are no studies comparing these two protocols. Study design, size, duration This prospective observational study included 163 patients. All the patients underwent artificial frozen-thawed embryo transfer cycles. Group 1 (n = 43), the control group, did not get additional therapy. Group 2 (n = 46) received intrauterine G-CSF (300 mcg) perfusion on 5-6 and 8-9 days of cycle. Group 3 (n = 74) received intrauterine PRP (5-7 ml) perfusion on 8-9, 10-11 and 12-13 days of cycle. The study was carried out between December 2017 and December 2019. Participants/materials, setting, methods Inclusion criteria: age 20-42 years; BMI 18-30 kg/m2; endometrial thickness on embryo transfer (ET) day ≤ 7mm in previous cycles; previous non-effective ET cycles; good quality embryos (Gardner and Schoolcraft classification). Exclusion criteria: uterine fibroids ≥4 cm; deep endometriosis; Asherman syndrome; allergic reaction to G-CSF. PRP was prepared by the double centrifugation technique (Beckman, USA). From 400 ± 50 ml of whole blood was made 40 ± 5 ml PRP with 0,6-0,7 x 1011 platelets. Main results and the role of chance Endometrial thickness on ET day in Group 1 was 7,0±1,1 mm, in Group 2 – 7,9±1,8 mm, in Group 3 – 8,0±1,3 mm. The difference was statistically significant between Group 1 and 2 – p = 0,003 (MD-0,96; 95% CI: 0,33; 1.59), between Group 1 and 3 – p = &amp;lt;0,001 (MD-1,0; 95% CI: 0,53; 1,47). No statistically significant difference was between Group 2 and 3 – p = 0,790 (MD-0,004; 95% CI: -0,53; 0,61). FET cycle cancelled due to thin endometrium occurred in 26 (60,5%), 18 (39,1%) and 13 (17,6%) patients in Groups 1,2 and 3 respectively. Pregnancy rate was statistically significant different between Group 1 and 2 – p = 0,005 (5,9% (1/17) vs. 46,4% (13/28), OR-0,07; 95%CI: 0,01; 0,62), between Group 1 and 3 – p = 0,007 (5,9%(1/17) vs. 41,0%(25/61), OR-0,09; 95%CI: 0,01; 0,72). No statistically significant difference was between Group 2 and 3 in pregnancy rate – p = 0,630 (46,4% (13/28) vs. 41,0% (25/61)). There was statistically significant difference in livebirth rate between Group 1 and 2 – p = 0,003 (0 (0/17) vs. 39,3% (11/28), between Group 1 and 3 – p = 0,014 (0 (0/17) vs. 27,9% (17/61). No statistically significant difference was in livebirth rate between Group 2 and 3 – p = 0,282 (39,3% (11/28) vs. 27,9% (17/61)). Limitations, reasons for caution Our study was carried out in a relatively small subset of patients; also in our study we investigated only FET cycles. There should be larger trials in future, including fresh embryo transfer cycles. Wider implications of the findings This study opens new possibilities in management of patients with thin endometrium. Trial registration number N/A

P-787 Factors associated with live birth rate (LBR) and multiple live birth rate (mLBR): UK vs France registries

Abstract Study question Do the associations between age, previous attempts, frozen and day-5 transfers relative to LBR and mLBR differ between national registries (UK vs France)? Summary answer Both registries agree age negatively correlates with LBR and mLBR; disagree on effects of frozen transfers, previous attempts and day-5 transfers on LBR and mLBR. What is known already Due to the high risks of multiple pregnancy, the focus of ART success was shifted from having a high number of live birth rate (LBR) to one full-term, healthy baby and a low multiple live birth rate (mLBR). Elective single embryo transfer (eSET) has been an effective strategy for reducing the risk of mLBR but in most guidelines, it is recommended for young patients (&amp;lt;35 years) only. There is extensive evidence from large-scale studies characterising how factors, seen in eSET policies, affect LBR. However, only a few studies focus on mLBR. Study design, size, duration A retrospective analysis of two national registry datasets, HFEA (UK) (N = 442042; 2014-2018) and ABM (France) (N = 305142; 2014-2018), evaluating how age (&amp;lt;35 yrs, 35-37 yrs, 38-40 yrs, &amp;gt;41 yrs), fresh/frozen embryo transfer (ET), previous attempts (0, 1, 2, 3, 4, 5 attempts), and embryo stage (day-5 or day-3 transfers) impact LBR and mLBR following eSET (control group) and multiple embryo transfer (MET) (treatment group). Participants/materials, setting, methods Statistical analyses of the datasets were conducted using adjusted two-sided odds ratios from chi-squared tests with 95% confidence intervals (α = 0.05) with Bonferroni correction. Main results and the role of chance Two registries agreed on the negative correlation between age and LBR (HFEA: eSET OR:1.00-0.79-0.73-0.57, p &amp;lt; 0.001; MET OR:1.00-0.85-0.74-0.55, p &amp;lt; 0.001; ABM: eSET OR:1.00-0.75-0.71-0.52, p &amp;lt; 0.001; MET OR:1.00-0.80-0.69-0.50, p &amp;lt; 0.001) and mLBR following MET (HFEA OR:1.00-0.79-0.70-0.71, p &amp;lt; 0.001; ABM OR:1.00-0.74-0.74-0.59, p &amp;lt; 0.001). mLBR following eSET remained constant with increasing age in both datasets (HFEA OR:1.00-0.91-0.92-1.34, NS; ABM OR:1.00-0.87-1.02-1.13, NS). LBR was significantly higher for fresh vs frozen eSET in both datasets (HFEA OR:1.36, p &amp;lt; 0.001; ABM OR:1.83, p &amp;lt; 0.001). However, HFEA showed no significant difference in LBR between fresh and frozen MET (OR:0.98, NS), whereas LBR in fresh MET was significantly higher in ABM (OR:1.28, p &amp;lt; 0.001). There was disagreement on fresh vs frozen ET mLBR (HFEA: eSET OR:1.10, NS; MET OR:0.97, NS; ABM: eSET OR:0.81, p &amp;lt; 0.05; MET OR:1.36, p &amp;lt; 0.001). Registry results differed regarding the impact of previous attempts on LBR and mLBR.Day-5 ETs had significantly higher LBR compared to day-3 (HFEA eSET OR:1.29, p &amp;lt; 0.001; MET OR:1.37, p &amp;lt; 0.001; ABM: eSET OR:1.50, p &amp;lt; 0.001; MET OR:1.35, p &amp;lt; 0.001). mLBR was significantly higher following day-5 MET (HFEA OR:1.59, p &amp;lt; 0.001; ABM OR:1.27, p &amp;lt; 0.001) but only significantly higher following eSET in the French registry (HFEA OR:0.64, NS; ABM OR:1.40, p &amp;lt; 0.01). Limitations, reasons for caution Limitations included selection bias due to the retrospective design of the study, as a result, the populations include predominantly caucasian, European populations. The conclusions drawn relate to the practices from particular countries, so it is important to evaluate multiple, more diverse datasets. Wider implications of the findings It is encouraging that both registries agreed on the effects of age, whilst remaining factors were not generalizable and require further assessment. This study demonstrated that even large, national registries contain inherent biases and policymakers should not draw policies based on one dataset, especially when prospective trial is not feasible. Trial registration number N/A

First clinical report of 179 surrogacy cases in the UK: implications for policy and practice

Research questionWhat implications for policy and practice can be derived from outcomes and trends observed across 8 years of a surrogacy programme in two UK-regulated IVF centres (London, Cardiff)? DesignRetrospective cohort study analysing surrogacy treatments undertaken between 2014 and September 2021. ResultsSurrogacy continues to rise in popularity in the UK despite the inability of those supporting safe and professional practice to advertise to recruit surrogates. In two IVF centres regulated by the Human Fertilisation and Embryology Authority (HFEA), both the number of surrogacy treatments and the proportion of those undertaken on behalf of same-sex male intended parents increased year on year in the period studied. From a cohort of 108 surrogates, 71 babies were born to 61 surrogates (with five pregnancies ongoing) by February 2022. No statistically significant difference in live birth rates (LBR) was observed between the heterosexual couples and same-sex male couples. Sample sizes of single and transgender intended parents were too small (n < 5) to compare. The use of vitrified oocytes in surrogacy treatments has increased year on year, while fresh oocyte use has declined since peaking in 2019. There was no significant difference in LBR between fresh and vitrified oocyte usage across the cohort. ConclusionsThe number of surrogacy treatments steadily increased, with clear evidence that the proportion of same-sex male couples accessing surrogacy is a major contributor to this growth. Vitrified/warmed oocyte use now outstrips the use of fresh oocytes in the surrogacy treatment cycles studied here. The results represent a strong basis for supporting the liberalization of regulatory reform expected to be introduced in the UK later in 2022.

Endometriosis and oocyte quality: an analysis of 13 614 donor oocyte recipient and autologous IVF cycles.

STUDY QUESTIONDoes endometriosis affect live birth following donor oocyte recipient versus autologous IVF?SUMMARY ANSWERThere was no significant difference in the live birth rate (LBR) in women with endometriosis undergoing donor oocyte recipient cycles versus autologous IVF cycles.WHAT IS KNOWN ALREADYFor infertile women with endometriosis, IVF is often considered as a treatment option. Lower implantation and pregnancy rates have been observed following IVF in women with endometriosis. It has been debated whether the lower pregnancy rate is due to the effect on oocyte quality or the endometrium, thus affecting implantation. To delineate whether endometriosis affects oocyte quality or the endometrium, we planned a study, using a donor oocyte recipient model, where the recipients were women diagnosed with endometriosis and compared their outcomes with women who underwent autologous IVF, who had also been diagnosed with endometriosis.STUDY DESIGN, SIZE, DURATIONHuman Fertilization and Embryology Authority (HFEA) anonymized data from 1996 to 2016 were analyzed. This comprised of a total of 758 donor oocyte recipients, where the recipients were women diagnosed with endometriosis, and 12 856 autologous IVF cycles where the women were diagnosed with endometriosis as the sole cause of infertility.PARTICIPANTS/MATERIALS, SETTING, METHODSData on all women with endometriosis undergoing donor oocyte recipient and autologous IVF cycles were analyzed to compare live birth outcomes. Logistic regression analysis was performed adjusting for number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer, number of embryos transferred and fresh or frozen embryo transfer cycle.MAIN RESULTS AND THE ROLE OF CHANCEThere was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles compared to women undergoing autologous IVF fresh embryo transfer cycles (31.6% vs 31.0%; odds ratio (OR) 1.03, 99.5% CI 0.79–1.35). After adjusting for confounders, there was no significant difference in LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles versus autologous fresh embryo transfer cycles (adjusted OR (aOR) 1.05, 99.5% CI 0.79–1.41).There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient frozen embryo transfer cycles compared to women undergoing autologous frozen embryo transfer cycles (19.6% vs 24.0%; OR 0.77, 99.5% CI 0.47–1.25). After adjusting for potential confounders, there was no significant difference in the LBR in women undergoing donor oocyte recipient frozen embryo transfer cycles compared with autologous frozen embryo transfer cycles (aOR 0.85, 99.5% CI 0.51–1.41).LIMITATIONS, REASONS FOR CAUTIONAlthough the analysis was adjusted for potential confounders, there was no information on the extent and classification of endometriosis as well as oocyte number. Furthermore, adenomyosis is thought to co-exist in women with endometriosis and may have independent pathophysiological mechanisms affecting fertility, for which there was no information.WIDER IMPLICATIONS OF THE FINDINGSThe study shows no difference in LBR between donor oocyte recipient cycles in which all recipients had endometriosis compared to autologous IVF cycles in women with endometriosis. Therefore, this study finding suggests that there may be a minimal or no effect of oocyte quality on IVF outcomes in women with endometriosis.STUDY FUNDING/COMPETING INTEREST(S)No funding was obtained. M.S.K. is an associate editor with Human Reproduction Open. He was not involved in the editorial or peer review process for the manuscript.TRIAL REGISTRATION NUMBERN/A.

A comparison of frozen-thawed embryo transfer protocols in 2920 single-blastocyst transfers.

To assess the effect of frozen-thawed embryo transfer (FET) protocol on live-birth rate (LBR) and clinical pregnancy rate (CPR), in single-vitrified-blastocyst transfer MATERIALS AND METHODS: Retrospective cohort study with FET of a single-blastocyst embryos (n = 2920 cycles) thawed 2013-2018. FET protocols were natural cycles (NC-FET) (n = 147), artificial hormone replacement treatment cycles (HRT-FET) (n = 2645), and modified NC (mNC) with hCG triggering (n = 128). Primary outcome was LBR. Adjustment for age, embryo grade, year of freezing\thawing, infertility cause, and endometrial thickness was performed. There were no significant differences between the groups with regard to female age, embryo grade, and endometrial thickness. LBR was higher in the mNC compared to HRT-FET cycles (38.3% vs. 20.9% P < 0.0001), and in the NC compared to HRT-FET cycles (34.7% vs. 20.9%, P = 0.0002). CPR was higher in the mNC compared to HRT-FET cycles (46.1% vs. 33.3% P = 0.0003), and in the NC compared to HRT-FET cycles (45.9% vs. 33.3%, P = 0.002). There was no significant difference in LBR or CPR between NC-FET and mNC-FET. Higher LBR with NC-FET and mNC-FET remained significant after adjusting for confounders (aOR 2.42, 95%CI 1.53-3.66, P < 0.0001). The use of the convenient artificial HRT-FET cycles must be cautiously reconsidered in light of the potential negative effect on LBR when compared with natural cycle FET.

Elevated Body Mass Index in Donor Oocyte Recipients Does Not Affect Implantation of Euploid Embryos.

Background: Obesity is a worldwide epidemic that has been shown to have serious implications on health outcomes. Regarding reproductive health, increased body mass index (BMI) reduces fertility and increases the time to conceive. It is unclear how excess weight in females affects the development of oocytes and embryos or the impact of implantation. Materials and Methods: This retrospective single-center study aimed to determine if overweight and obese oocyte recipients had similar pregnancy outcomes compared with healthy weight controls after the transfer of a single euploid frozen-thawed embryo transfer (FET). Five hundred twenty-eight patients who underwent a transfer from 2016 to 2021 were included. The primary outcome studied was the clinical pregnancy (CP) rate. Secondary outcomes included live birth (LB) rate, biochemical pregnancy loss (BPL) rate, and clinical pregnancy loss (CPL) rate. Results: The overall CP rate was 54.9% and did not differ significantly among normal weight (n = 318), overweight (n = 129), and obese (n = 81) BMI categories (0.56 vs. 0.56 vs. 0.49, p = 0.56). There were no significant differences in LB rate (0.47 vs. 0.43 vs. 0.38, p = 0.33), BPL rate (0.14 vs. 0.09 vs. 0.11, p = 0.59), and CPL rate (0.15 vs. 0.21 vs. 0.18, p = 0.38) among BMI groups. Conclusions: Our findings provide support that BMI alone does not adversely alter endometrial receptivity and is not the cause of poor in vitro fertilization (IVF) outcomes in patients with increased BMI. These deleterious IVF outcomes might be to the result of diminished oocyte and/or embryo quality or other factors that have not yet been elucidated.

Does Post-Warming Extended Culture Duration Affect the Clinical and Obstetric Outcomes of Patients of Advanced Maternal Age? A Single-Center Study.

BackgroundThe single vitrified-warmed blastocyst transfer (SVBT) cycle has been increasingly utilized for assisted reproductive technology. Women of advanced maternal age (AMA) comprise a significant portion of patients who have undergone ‘freeze-all’ cycles. This study investigated the association between the post-warming extended culture duration and pregnancy outcomes in patients of AMA.MethodsThis retrospective cohort study analyzed the outcomes of 697 SVBT cycles between January 2016 and December 2017. The cycles were divided into 3 groups based on the age of the female partners: group I: < 35 years (n = 407), group II: 35–37 years (n = 176); and group III, 38–40 years (n = 114). Data are shown as the mean ± standard error of the mean. Data were analyzed using one-way ANOVA followed by Duncan’s multiple range test. Statistical significance was set at P < 0.001.ResultsThe blastocyst rate, clinical pregnancy rate, and live birth rate (LBR) was significantly lower in the AMA groups. However, there were no significant differences in LBR in the transfer between the AMA and younger groups according to blastocyst morphology and post-warming extended culture duration.ConclusionPost-warming extended culture of blastocysts is not harmful to patients of AMA. It could be a useful parameter in clinical counseling and decision making for fertility treatments.

P-295 Does endometriosis affect oocyte quality? An analysis of 13 627 donor oocyte recipient and autologous IVF cycles

Abstract Study question Does endometriosis affect live birth following donor oocyte recipient versus autologous in vitro fertilisation (IVF) cycle. Summary answer There was no significant difference in the live birth rate (LBR) in women with endometriosis undergoing donor oocyte recipient versus autologous IVF cycle. What is known already For infertile women with endometriosis, IVF is often considered as a treatment option. Lower implantation and pregnancy rates have been observed following IVF in women with endometriosis when compared to tubal factor infertility. It has been debated that lower pregnancy rates following IVF in endometriosis is due to both oocyte quality and the endometrium. To delineate whether endometriosis affects oocyte quality or the endometrium, we planned a study using donor oocyte recipient model where the recipient were women with endometriosis. We compared the LBR after oocyte recipient cycle with autologous IVF in women with endometriosis Study design, size, duration We obtained anonymised dataset of all the IVF cycles performed in the UK since 19991 from the Human Fertilization and Embryology Authority (HFEA). Data from 1996 to 2016 comprising a total of 13 627 donor oocyte recipient and autologous IVF cycles with endometriosis and no other cause of infertility were analysed. Participants/materials, setting, methods Data on all women with endometriosis undergoing fresh or frozen IVF treatment cycles were analysed to compare the LBR between donor oocyte recipient and autologous treatment cycles. Logistic regression analysis was performed adjusting for number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer, number of embryo transferred, fresh and frozen cycle. Main results and the role of chance There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh cycles compared to women undergoing fresh autologous IVF cycles (31.6% vs. 31.0%; odds ratio, OR 1.03, 99% CI 0.79 – 1.35). After adjusting for confounders listed above, there was no significant difference in LBR in women undergoing donor oocyte recipient fresh cycles versus fresh autologous ART cycles (aOR 1.06, 99% CI 0.79 – 1.42). There was no significant difference in the LBR in women with endometriosis undergoing frozen donor oocyte recipient cycles compared to women undergoing autologous frozen embryo transfer cycles (19.6% vs. 24.0%; OR 0.77, 99% CI 0.47 - 1.25). After adjusting for potential confounders, there was no significant difference in the LBR in women undergoing frozen donor oocyte recipient cycles compared with autologous frozen embryo transfer cycles (aOR 0.84, 99% CI 0.50 - 1.41). Limitations, reasons for caution Although the analysis was adjusted for several potential confounders, there was no information on classification of endometriosis to allow adjustment. Wider implications of the findings The current study design does not indicate endometriosis has an impact on oocyte quality given that the outcomes in donor oocyte recipient cycles are comparable with autologous IVF cycles. These findings need to be further studied and validated. Trial registration number Not applicable

P–295 Does endometriosis affect oocyte quality? An analysis of 13 627 donor oocyte recipient and autologous IVF cycles

Abstract Study question Does endometriosis affect live birth following donor oocyte recipient versus autologous in vitro fertilisation (IVF) cycle. Summary answer There was no significant difference in the live birth rate (LBR) in women with endometriosis undergoing donor oocyte recipient versus autologous IVF cycle. What is known already For infertile women with endometriosis, IVF is often considered as a treatment option. Lower implantation and pregnancy rates have been observed following IVF in women with endometriosis when compared to tubal factor infertility. It has been debated that lower pregnancy rates following IVF in endometriosis is due to both oocyte quality and the endometrium. To delineate whether endometriosis affects oocyte quality or the endometrium, we planned a study using donor oocyte recipient model where the recipient were women with endometriosis. We compared the LBR after oocyte recipient cycle with autologous IVF in women with endometriosis Study design, size, duration We obtained anonymised dataset of all the IVF cycles performed in the UK since 19991 from the Human Fertilization and Embryology Authority (HFEA). Data from 1996 to 2016 comprising a total of 13 627 donor oocyte recipient and autologous IVF cycles with endometriosis and no other cause of infertility were analysed. Participants/materials, setting, methods Data on all women with endometriosis undergoing fresh or frozen IVF treatment cycles were analysed to compare the LBR between donor oocyte recipient and autologous treatment cycles. Logistic regression analysis was performed adjusting for number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer, number of embryo transferred, fresh and frozen cycle. Main results and the role of chance There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh cycles compared to women undergoing fresh autologous IVF cycles (31.6% vs. 31.0%; odds ratio, OR 1.03, 99% CI 0.79 – 1.35). After adjusting for confounders listed above, there was no significant difference in LBR in women undergoing donor oocyte recipient fresh cycles versus fresh autologous ART cycles (aOR 1.06, 99% CI 0.79 – 1.42). There was no significant difference in the LBR in women with endometriosis undergoing frozen donor oocyte recipient cycles compared to women undergoing autologous frozen embryo transfer cycles (19.6% vs. 24.0%; OR 0.77, 99% CI 0.47 - 1.25). After adjusting for potential confounders, there was no significant difference in the LBR in women undergoing frozen donor oocyte recipient cycles compared with autologous frozen embryo transfer cycles (aOR 0.84, 99% CI 0.50 - 1.41). Limitations, reasons for caution Although the analysis was adjusted for several potential confounders, there was no information on classification of endometriosis to allow adjustment. Wider implications of the findings: The current study design does not indicate endometriosis has an impact on oocyte quality given that the outcomes in donor oocyte recipient cycles are comparable with autologous IVF cycles. These findings need to be further studied and validated. Trial registration number Not applicable

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

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

P–426 Uterine Natural Killer Cells in Recurrent Miscarriage and Implantation Failure: An Updated Systematic Review and Meta-analysis

Abstract Study question Do women with recurrent miscarriage (RM) or implantation failure (RIF) have different levels of uterine Natural Killer (NK) cells compared to fertile controls? Summary answer Women with RIF but not RM are associated with significantly higher levels of CD56+ uterine NK cells compared to controls. What is known already Uterine NK cells (uNK) are different from peripheral NK cells (pNK) and are important in early pregnancy for development of the placenta. The association between uNK and RM/RIF is less clear, but dysfunction of uNK is believed to result in early pregnancy failure. Previous systematic reviews by Seshadri (2014) and Tang (2013) on infertile and RM patients showed no significant difference in uNK levels and highlighted need for further studies. Since, many prospective studies have been published and therefore warrant an updated systematic review. On the other hand, evidence for correlation between uNK and pNK is sparse and needs clarification. Study design, size, duration We have conducted a systematic review and meta-analysis to evaluate three outcomes. The primary outcome was the difference of uNK level in RM/RIF compared to controls. The secondary outcome was livebirth rate in women with RM/RIF with high compared to normal uNK level, and the tertiary outcome was correlation between uNK and pNK in RM/RIF. Participants/materials, setting, methods The electronic database search included MEDLINE, EMBASE, Web of Science and bibliographies from included articles from inception to December 2020 using a combination of MESH and keywords. Search, screen, and data extraction were performed by two reviewers independently. Quality assessment was conducted with ROBINS-I and meta-analysis with Revman 5.3. Out of 4636 studies screened, 43 studies (2539 women) and 3 studies each (598 and 77 women) were analysed for primary, secondary and tertiary outcomes respectively. Main results and the role of chance Our meta-analysis showed that CD56+ uNK were significantly higher in women with RIF but not RM compared to controls (SMD 0.60; 95% CI 0.12–1.08]. Subgroup analysis in RM patients showed no significant difference whether definition of 2 or 3 previous RM was used, in primary/secondary RM compared to controls, or in primary versus secondary RM. CD56+ uNK were significantly higher in RM/RIF when sampled during mid-luteal phase [SMD 0.56; 95% CI 0.19–0.93] but not in the early pregnancy decidua. Interestingly, there was significant difference in CD56+ uNK when analysed by immunohistochemistry [SMD 0.50; CI 0.05–0.94] but not by flow cytometry, and when CD56+ uNK were reported as percentage over total endometrial cells [SMD 0.58; 95% CI 0.10–1.07]. Further subgroup analysis showed significant difference in CD16 + [SMD 0.54; 95% CI 0.18–0.89] but not in CD56+CD16-, CD56+CD16+ or CD57. For pregnancy outcome, there was no significant difference in livebirth rate in RM/RIF patients with high uNK compared to normal uNK [RR 1.06, 95% CI 0.86–1.30]. Mean uNK level in RM patients with subsequent miscarriage was not significantly higher than subsequent livebirth. Finally, the pooled correlation between CD56 pNK and CD56 uNK (r = 0.42; 95% CI –0.04–0.73] was not significant in RM/RIF patients. Limitations, reasons for caution The meta-analysis is limited by quality of some of the studies. Some data were presented in median that was transformed to mean which may result in data skew. Other confounding factors e.g. maternal age, fetal karyotype, number of previous miscarriages and variable definition of controls may contribute to bias. Wider implications of the findings: Clinical interpretation of uNK level needs to be treated with caution because there is significant heterogeneity in method of analysis. There may be a role for uNK measurement in RIF patients however further studies to understand pathophysiology underlying elevated uNK is warranted before recommending it as a diagnostic tool. Trial registration number N/A