Assisted Reproductive Technology Cycles Research Articles

State insurance mandates and racial and ethnic inequities in assisted reproductive technology utilization

ObjectiveTo examine whether the (1) scope of state-mandated insurance coverage for assisted reproductive technology (ART), and (2) proportion of the population eligible for this coverage, are associated with reductions in racial/ethnic inequities in ART utilization. DesignNational cross-sectional, ecologic study. SubjectsWe employed estimates from the U.S. Census Bureau of all women 20–44 years of age living in the U.S. in 2018. The number of women who initiated an ART cycle during that year that was reported to the U.S. Centers for Disease Control and Prevention (CDC) was obtained from the National ART Surveillance System (NASS). ExposureState mandates were classified by scope of required coverage for fertility services: Comprehensive, Limited, and No Mandate. Main Outcomes MeasuresRace and ethnic-specific ART utilization rates, defined as number of women undergoing ≥1 ART cycles per 10,000 women, were the primary outcome. As state mandates do not apply to all insurance plans, Comprehensive Mandate utilization rates were recalculated using denominators corrected for the estimated proportions of populations eligible for coverage. ResultsAcross all mandate categories, Non-Hispanic (NH) Asian and NH White populations had the highest ART utilization rates, whereas the lowest rates were among Hispanic, NH Black, and NH Other/Multiple Races populations. As compared to the NH Asian reference group, the NH Black population had smaller inequities in the Comprehensive Mandate group than the No Mandate group (Rate Ratio [RR 0.33 [0.28-0.38] versus RR 0.23 [0.22-0.24]). Using the Comprehensive Mandate group for each race/ethnicity as reference, the NH Black and NH Other/Multiple Races populations had the largest relative differences in utilization between the No Mandate and Comprehensive Mandate groups (RR 0.39 [0.37-0.41] and 0.33 [0.28-0.38], respectively). Within the Comprehensive Mandate group, the disparities in the Hispanic and NH Black populations moved towards the null after correcting for state-mandated insurance eligibility. ConclusionsRacial/ethnic inequities in ART utilization were reduced in states with comprehensive infertility coverage mandates. Inequities were further attenuated after correcting for mandate eligibility. Mandates alone, however, were not sufficient to eliminate disparities. These findings can inform future strategies aimed at improving ART access under a social justice framework.

Can endometrial compaction predict live birth rates in assisted reproductive technology cycles? A systematic review and meta-analysis.

Endometrial compaction (EC) is defined as the difference in endometrial thickness from the end of the follicular phase to the day of embryo transfer (ET). We aimed to determine the role of EC in predicting assisted reproductive technology (ART) success by conducting a meta-analysis of studies reporting the association between EC and clinical outcomes of ART. MEDLINE via PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the date of inception to May 19, 2023. The primary outcome was live birth rate (LBR) per ET. Secondary outcomes were live birth or ongoing pregnancy per ET, ongoing pregnancy per ET, clinical pregnancy per ET, and miscarriage per clinical pregnancy. Fifteen studies were included. When data from all studies reporting live birth were pooled, overall LBR rates were comparable in cycles showing EC or not [RR = 0.97, 95%CI = 0.92 to 1.02; 10 studies, 11,710 transfer cycles]. In a subgroup of studies that included euploid ET cycles, a similar LBR for patients with and without EC was noted [RR = 0.99, 95%CI = 0.86 to 1.13, 4 studies, 1172 cycles]. The miscarriage rate did not seem to be affected by the presence or absence of EC [RR = 1.06, 95%CI = 0.90 to 1.24; 12 studies]. The predictive value of EC in determining LBR is limited, and assessment of EC may no longer be necessary, given these findings. PROSPERO CRD42023410389.

Poor ovarian response in assisted reproductive technology cycles is associated with anti-ovarian antibody and pro-inflammatory immune responses

Anti-ovarian antibody (AOA) could be considered an independent marker for autoimmune ovarian disease and predicting future premature ovarian failure (POF). This study aims to investigate if AOA is associated with poor ovarian response (POR) and pro-inflammatory immune responses in women undergoing assisted reproductive technology (ART) cycles. Two hundred forty-eight women undergoing ART cycles were divided into four groups based on AOA test results and the presence of POR: POR(-)/AOA(-) group (N = 148), POR(+)/AOA(-) group (N = 34), POR (-)/AOA(+) group (N = 44), POR(+)/AOA(+) group (N = 22). The POR patients have a significantly higher prevalence of AOA than non-POR patients (P < 0.05). Peripheral blood CD56 + natural killer (NK) cell level (%), NK cytotoxicity, CD19 +CD5 + B-1 cell level (%), and IFN-γ/IL-10 producing T helper (Th) 1/Th2 cell ratios were significantly higher in POR(+)/AOA(+) group than those of other groups (P < 0.001, P < 0.005, P < 0.01, P < 0.05, respectively). TNF-α/IL-10 producing Th1/Th2 cell ratio of POR(+)/AOA(+) group was significantly higher than those of POR(+)/AOA(-) and POR(-)/AOA(-) groups (P < 0.05, respectively). Homocysteine and vitamin D levels of the POR(+)/AOA(+) group were significantly lower than those of other groups (P < 0.005, respectively). Plasminogen activator inhibiter-1 (PAI-1) level of POR(+)/AOA(+) group was significantly higher than that of POR(-)/AOA(-) group (P < 0.05). In the POR(+)/AOA(+) group, the prevalence of antiphospholipid antibodies was significantly higher than that of the POR(+)/AOA(-) group (P = 0.005). Women with autoimmune POR (POR(+)/AOA(+)) have dysregulated pro-inflammatory immune responses and metabolic factors. The diagnostic and therapeutic approaches for autoimmune POR should be differentiated from those for non-autoimmune POR.

Does the decrease in E2 levels between the trigger of ovulation and embryo transfer affect the reproductive outcome in IVF-ICSI cycles?

This study aimed to evaluate the effect of the rate of decline in serum estradiol (E2) levels between hCG injection and the day of embryo transfer (ET) on the success of assisted reproductive technology (ART) in women with infertility of different etiologies. Women 20-45 years of age who underwent a standard GnRH antagonist or long agonist protocol and fresh ET during day 3 of their first ART cycle were included. Group 1 was diagnosed with low ovarian reserve, group 2 comprised high ovarian responders, and group 3 consisted of normal responders. Both groups were divided into four subgroups according to the decrease in E2 levels between the day of hCG injection and the day of ET. Subgroup A patients had a decrease of <20%, subgroup B a decrease of 20-40%, subgroup C a decrease of 41-60%, and subgroup D a decrease >60%. The primary outcome measure was the effect of an E2 decline, based on the measurement of E2 on the day of hCG administration and day of ET, on the implantation rate. The secondary outcome was the change in E2 values in these three groups. The study was conducted on 1.928 women. Of these, 639 were poor responders (group 1), 502 were high responders (group 2), and 787 women had a normal ovarian response (group 3). Patients with a 60% decrease in their E2 levels on the ET day after hCG had a lower live birth rate (LBR) and higher miscarriage rate (MCR), except normoresponders, in whom a similar decline was significant only with respect to MCR. We indicate that high ovarian responders who underwent fresh ET cycles with a 60% decrease in their E2 levels on the ET day after human chorionic gonadotropin had lower LBRs and higher miscarriage. However, in normoresponder women, this decline was only significant in miscarriage.

Fertility preservation after gonadotoxic treatments for cancer and autoimmune diseases

BackgroundThe indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation.MethodsWe conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome.ResultsForty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29–37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1–4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5–14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15–1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15–4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5–100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0–100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births.ConclusionsOocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.

A Geospatial Analysis of Disparities in Access to Oncofertility Services

Fertility preservation (FP), including oocyte and embryo cryopreservation prior to gonadotoxic therapy, is an urgent and essential component of comprehensive cancer care. Geographic proximity to a center offering FP is a critical component of ensuring equitable access for people with cancer desiring future fertility. To characterize the distribution of centers offering FP services in the US, quantify the number of self-identified reproductive-age female individuals living outside of geographically accessible areas, and investigate the association between geographic access and state FP mandates. This cross-sectional analysis calculated 2-hour travel time isochrone maps for each center based on latitude and longitude coordinates. Population-based geospatial analysis in the US was used in this study. Fertility clinics identified through the 2018 Centers for Disease Control and Prevention Fertility Clinic Success Rates Report were defined as oncofertility centers by meeting 4 criteria: (1) offered oocyte and embryo cryopreservation, (2) performed at least 1 FP cycle in 2018, (3) served people without partners, and (4) had an accredited laboratory. County-level data were obtained from the 2020 US Census, with the primary at-risk population identified as reproductive-age female individuals aged 15 years to 44 years. The analysis was performed from 2021 to 2022. Location outside of 2-hour travel time isochrone of an oncofertility center. Oncofertility centers were compared with centers not meeting criteria and were classified by US region, state FP mandate status, number of assisted reproductive technology cycles performed, and number of FP cycles performed. The number and percentage of at-risk patients, defined as those living outside of accessible service areas by state, were identified. Among 456 Centers for Disease Control and Prevention-reporting fertility clinics, 86 (18.9%) did not meet the criteria as an oncofertility center. A total of 3.63 million (5.70%) reproductive-age female individuals lack geographic access to an oncofertility center. States with FP mandates have the highest rates of eligible female patients with geographic access (98.54%), while states without active or pending legislation have the lowest rates (79.57%). The greatest disparities in geographic access to care are most concentrated in the Mountain West and West North Central regions. Patients face numerous barriers to comprehensive cancer care, including a lack of geographic access to centers capable of offering FP services. This cross-sectional study identified disparities in geographic access and potential opportunities for strategic expansion.

Ovarian Follicular Response Is Altered by Salpingectomy in Assisted Reproductive Technology: A Pre- and Postoperative Case-Control Study.

Objectives: The goal of this study was to assess the effect of unilateral salpingectomy on the number of mature follicles in the ipsilateral ovary during an assisted reproductive technology (ART) stimulation cycle, as compared to the contralateral ovary. Methods: This was a retrospective, single-center, case-control cohort study conducted from 2017 to 2022. Patients from 18 to 43 years old who underwent at least one ART cycle before and after a unilateral salpingectomy were included. The number of recruited follicles, including mature (≥16 mm) and intermediate follicles (13-15.5 mm), on the salpingectomy side (case) were compared to those present on the contralateral ovary (control) during an ART attempt. To take into account the inter-ovarian variability, the comparison was performed on two ART cycles, performed before then after the salpingectomy. Results: Overall, 24 patients were included in our study. While the number of mature follicles was similar in both ovaries before surgery, the mean number of mature follicles was significantly reduced after salpingectomy in the operated side, as compared to the control side, being, respectively 3.00 vs. 5.08 (p = 0.048). There was no significant difference between the intermediate and total recruited follicles. Conclusions: Our study suggests that salpingectomy may impact the follicle recruitment on the ipsilateral side by altering the vascularization during mesosalpinx coagulation. Gynecologists should be mindful of this concept and accurately set surgical indications. Beyond the indication, this emphasizes the critical role of having infertility surgeons sensitive to fertility preservation for optimal management of ART patients. Further studies with larger patient populations are required to confirm these results.

Pregnancy Outcomes of Assisted Reproductive Technology (ART) Cycle Complicated by Ovarian Hyperstimulation Syndrome (OHSS): Case Series Study.

Ovarian hyperstimulation syndrome (OHSS) is a frequent, potentially lethal side effect of assisted reproductive technology (ART), distinguished by symptoms such as ovarian enlargement, ascites, and pleural effusion. This study is designed to study the effect of assisted reproductive technology (ART) cycle complicated by OHSS on pregnancy outcomes. A case series study at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia, was executed to examine the pregnancy outcomes in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles. Fifteen patients were admitted to the IVF unit between January 2015 and December 2021. Data were retrieved from patients' medical records, and descriptive statistical methods were employed to analyze participants' data. The study assessed pregnancy outcomes for 15 female participants (mean age=31.1 years, SD=3.46) with a BMI range of 20-40 (mean BMI=29.6, SD=6.4), of whom 33.3% were classified as obese. The primary factor of infertility was anovulation (66.7%), followed by male factors (20%). About 26.7% of those affected by OHSS had moderate OHSS, and 73.3% had severe OHSS, with 100% of those with severe OHSS having undergone three embryo transfers. None of the participants developed gestational diabetes mellitus (DM), but one participant had high blood sugar levels (6.67% of total participants), with a mean glucose of 6.3±2.0. There were no instances of preeclampsia, gestational hypertension, abnormal placentas, or congenital abnormalities in newborns among the participants. Preterm deliveries were common, with 33.3% delivering between 32 and 37 weeks, 6.7% before 28 weeks, and 33.3% within 28-32 weeks. Overall, 73.3% of the participants experienced pregnancy, and the birth mode was almost evenly split between vaginal and cesarean birth. In conclusion, this research provides an exploration into the outcomes of pregnancies in women undergoing assisted reproductive technology treatments complicated by ovarian hyperstimulation syndrome. It shows anovulation as a prevalent cause of infertility and a noteworthy incidence of severe OHSS. Despite these challenges, a significant number of women were able to experience pregnancy, although preterm deliveries and abortions were common. The delivery methods were fairly balanced between vaginal birth and cesarean section. These findings underscore the necessity for more effective strategies to manage OHSS and improve pregnancy outcomes in ART procedures.

Evaluation of costs associated with fertility treatment leading to a live birth after one fresh transfer: A global perspective.

Considerable costs are associated with infertility treatment, but little evidence is available on the main drivers of treatment costs. This cost analysis investigated key costs for treatment with assisted reproductive technology (ART) and the proportion of costs attributed to the acquisition of recombinant human follicle-stimulating hormone (r-hFSH) alfa originator for one fresh embryo transfer (ET) leading to a live birth in Spain, Norway, the UK, Germany, Denmark, South Korea, Australia, and New Zealand. The total costs for one ART cycle with a fresh ET leading to a live birth varied between countries (€4108-€12,314). Costs for pregnancy and live birth were the major contributors in European countries, and the costs of oocyte retrieval, monitoring during ovarian stimulation, pregnancy, and live birth were the top contributors in the Asia-Pacific countries, included in this analysis. Acquisition costs for r-hFSH alfa originator contributed to only 5%-17% of the total costs of one ART cycle with one fresh ET leading to a live birth.

The Sperm DNA Fragmentation Assay with SDF Level Less Than 15% Provides a Useful Prediction for Clinical Pregnancy and Live Birth for Women Aged under 40 Years.

This retrospective cohort study was conducted on 1148 males who presented along with their partners for infertility management at the PIVET Medical Centre between 2013 and 2022 and had a sperm DNA fragmentation (SDF) assay performed by Halosperm, thereafter participating in 1600 assisted reproductive technology (ART) cycles utilising one of three modalities, namely, IVF-Only, ICSI-Only or IVF-ICSI Split cycles. The outcomes from the ART cycles were then analysed as two groups based on SDF levels <15% and ≥15%. The study showed the unadjusted fertilization rates were not different between the groups, neither across the four female age ranges. However, when the fertilization rates were adjusted for the mature oocytes (metaphase-II oocytes), there was a highly significant difference in fertilization rates in favour of the group with SDF levels < 15% where the women were in the younger age grouping of <35 years (78.4% vs. 73.0%; p < 0.0001). Overall, there was no difference in the rates of blastocyst development nor clinical pregnancy rates between the two SDF groups, but there was a significantly higher pregnancy rate for the younger women (<35 years) with the group of SDF level < 15% (44.1% vs. 37.4%; p = 0.04). Similarly, there was no difference in the miscarriage rates overall with respect to SDF groups, and no clear picture could be deciphered among the women's age groups. With respect to cumulative live births, this reflected the pregnancy rates with no overall difference between the two SDF groups, but there was a significantly higher cumulative live birth rate for women <35 years where the SDF level was <15% (38.6% vs. 28.6%; p < 0.01). Among the three modalities, the highest cumulative live birth rate occurred within the group with SDF level < 15%, being highest with the IVF mode, particularly for women aged <40 years (43.0% vs. 37.7% for IVF-ICSI Split and 27.9% for ICSI; p = 0.0002), noting that the IVF case numbers were disproportionately low.

The Effect of COVID-19 Severity, Associated Serum Autoantibodies and Time Interval after the Disease on the Outcomes of Fresh Oocyte ART Cycles in Non-Vaccinated Patients

It is assumed that SARS-CoV-2- and COVID-19-associated autoimmune processes may affect the outcomes of assisted reproductive technology (ART) cycles. This observational prospective study included 240 infertile patients: 105 patients had no history of COVID-19 (group 1) and 135 patients had experienced COVID-19 (group 2) in a mild (n = 85) or moderate (n = 50) form less than 12 months prior to oocyte retrieval. Using ELISAs, the profiles of their serum autoantibodies were determined, including antiphospholipid antibodies and antibodies to nuclear and thyroid antigens. The parameters of oogenesis and embryogenesis, as well as the pregnancy and childbirth rates, did not differ between groups 1 and 2, and also between the subgroups with different severities of COVID-19. However, when oocyte retrieval was performed less than 180 days after COVID-19, a higher proportion of poor-quality blastocysts was obtained (p = 0.006). A high risk of early miscarriage was found in the patients with moderate COVID-19. In group 2, IgG antibodies to annexin V, phosphatidylethanolamine (PE), and TSHr were detected more often than in group 1 (p = 0.035; p = 0.028; and p = 0.033, respectively), and a weak inverse correlation was revealed between anti-PE IgG and the number of oocytes and zygotes obtained. The results of the study suggest a possible adverse effect of COVID-19 and its associated autoantibodies on the outcomes of fresh oocyte ART cycles and early pregnancy, which depends on the severity of COVID-19 and the time interval after the disease.

Mapping international research output within ethical, legal, and social implications (ELSI) of assisted reproductive technologies.

Research about ethical, legal, and social implications (ELSI) of assisted reproductive technologies (ART) is influenced by cultural and value-based perspectives. It impacts regulations, funding, and clinical practice, and shapes the perception of ART in society. We analyze trends in the global literature on ELSI of ART between 1999 and 2019. As most output is produced by North America, Western Europe, and Australia, we focus on international research, i.e., academic articles studying a different country than that of the corresponding author. The corpus, extracted from PubMed, Web of Science, and Scopus, includes 7714 articles, of which 1260 involved international research. Analysis is based on titles, abstracts and keywords, classification into ART fields and Topic Modeling, the countries of corresponding author, and countries mentioned in abstracts. An absolute increase in the number of international studies, and their relative proportion. Trends of decentralization are apparent, yet geographic centralization remains, which reflects an unequal distribution of research funds across countries and may result in findings that do not reflect global diversity of norms and values. Preference for studying conceptual challenges through philosophical analysis, and for fields that concern only a portion of ART cycles. Less attention was dedicated to economic analysis and barriers to access, or to knowledge of and attitudes. International studies provide an opportunity to expand and diversify the scope of ELSI research. We call on the research community to promote international collaborations, focus on less explored regions, and divert more attention to questions of cost, access, knowledge, and attitudes.

Effects of Infertility Drug Exposure on the Risk of Borderline Ovarian Tumors: A Systematic Review and Meta-Analysis.

Whether infertility drug exposure increases the risk of borderline ovarian tumors (BOTs) remains controversial. The present study was conducted with a comprehensive search for studies published from January 1990 to December 2021 in the online databases Cochrane Library, PubMed, Web of Science and EMBASE. We considered the first diagnosis of a BOT as the primary outcome. The odds ratio (OR) was calculated with corresponding 95% confidence intervals (CIs) for the risk of BOTs in patients who were treated with infertility drugs. Ten studies, a total of 2,779,511 women, qualified for inclusion in this meta-analysis. The pooled OR of 1.56 (95% CI: 1.09-2.22) revealed a significant positive association between infertility drugs and an increased risk for BOTs, but for specific drugs, only CC plus Gn had statistical significance. No publication bias was detected using the Egger and Begg tests (p > 0.05). A significant difference in BOT incidence was observed among infertile women and nulliparous women who were treated with or without infertility drugs. In conclusion, the use of infertility drugs may increase the risk of BOTs, but a dose-dependent relationship was not observed between the number of assisted reproduction technology cycles and the risk of BOTs, and infertile women who successfully became pregnant might have a reduced risk. Registration: PROSPERO, CRD42022330775.

P-777 Can endometrial compaction predict live birth/ongoing pregnancy rates in assisted reproductive technology cycles? A systematic review and meta-analysis

Abstract Study question Can endometrial compaction (EC) predict live birth/ongoing pregnancy rates (LBR/OPR) in assisted reproductive technology (ART) cycles? Summary answer Our meta-analysis shows that LBR/OPRs are similar in cycles with or without EC. Analysis of studies with euploid embryo transfers (ETs) also yield similar LBR/OPR. What is known already EC is a novel concept, defined as a change in endometrial thickness (EMT) between the end of follicular phase and ET day. Early studies implied that EC can be a predictor for improved LBR/OPRs in ART. However, subsequent studies presented conflicting results. The role of EC in predicting ART success remains undetermined and there is paucity of data whether a subgroup of women exists for whom EC may be predictive for ART success. Study design, size, duration We performed a systematic review and meta-analysis of studies reporting LBR/OP with regard to EC. Two independent authors searched electronic databases from the date of inception until January 29, 2023. Primary outcome was LBR/OPR per ET. Secondary outcomes were clinical pregnancy (CP) and miscarriage rates per ET. For dichotomous outcome measures, Mantel-Haenszel risk ratios (RRs); with 95% CIs are presented. A fixed or random effects model was used based on heterogeneity of the data. Participants/materials, setting, methods Initial search yielded 4816 studies. After exclusion through titles, 81 studies were assessed by reading their abstracts. Full text of 22 studies were evaluated. Finally, 16 studies involving a total of 13976 cycles were included in the meta-analysis. Included studies were further scrutinized based on the definitions for EC, fresh or frozen-thawed ET, endometrial preparation methods and utilization of preimplantation genetic diagnosis. Data for primary and secondary outcomes were extracted by two authors independently. Main results and the role of chance In our meta-analysis of studies using a cut-off value of 5% change in EMT to define EC, LBR/OPR was similar in cycles with and without EC [RR = 1.10, 95%CI = 0.97 to 1.24; 11 studies, 6157 cycles]. When no cut-off was implemented and the minimum EMT changes were taken into account for each study, LBR/OPR rates were comparable between cycles showing EC or not [RR = 1.04, 95%CI = 0.96 to 1.12; 16 studies, 13976 cycles]. In concordance, analysis of the six studies with 2710 cycles reporting only euploid embryo transfers yielded similar LBR/OPR for cycles with and without EC [RR = 1.01, 95%CI = 0.90 to 1.12]. LBR/OPR was comparable for cycles demonstrating EC or not when only cycles with artificial hormonal preparation for frozen-thawed ET were analyzed [RR = 1.09, 95%CI = 0.97 to 1.21; 11 studies, 5811 cycles]. Regarding the secondary outcome parameters, with a cut-off of 5% change in EMT, clinical pregnancy rates [RR = 0.98, 95%CI = 0.90 to 1.07; 8 studies, 5578 cycles] and miscarriage rates [RR = 0.91, 95%CI = 0.69 to 1.19; 8 studies, 3413 cycles] were similar between compaction and no-compaction cycles. Limitations, reasons for caution Around 3/4 of the studies are retrospective. While most studies define EC as ≥ 5% change in EMT, some used 0% or 10%. Moreover, some studies presented data as “compaction” and “no compaction” while others preferred “compaction”, “same” and “expansion”. We combined “no change” and “expansion” groups as the ‘’non-compaction’’ group. Wider implications of the findings Once a promising predictor for ART success, EC does not seem to be helpful in predicting LBR/OPR and calculating EC may be obsolete. Moreover, analysis on euploid ETs imply that embryo, not EC, determines the outcome. Further studies, preferably on euploid ETs, with a homogeneous definition of EC are needed. Trial registration number Not applicablez

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 (&amp;gt;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 (&amp;gt;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-292 It is feasible to carry out a large-scale multi-national Assisted Reproductive Technology Real World Data (RWD) collection prospectively, encompassing collected patient and treatment cycle information

Abstract Study question Is it feasible to carry out a large-scale multi-national Assisted Reproductive Technology Real World Data (RWD) collection prospectively, encompassing collected patient and treatment cycle information? Summary answer The creation of an international database collecting RWD is feasible. The quality and quantity of the data allow them to be used for research purposes. What is known already Real World Evidence (RWE) may help to answer clinical research questions that are relevant to a broad population of patients. For 40 years, Assisted Reproductive Technology (ART) treatment cycle data have been collected in national registries. The aggregated national data are further collated on an international level. These data are useful for describing secular trends in ART utilization and associated outcomes. However, registries often fall short in providing patient-level and treatment-cycle-level information for data collation and analysis. Furthermore, national registries may restrict access of raw data for open research, for political, infrastructural, or legal reasons. Study design, size, duration In a first phase, the OPERA database (Observational retrospective ProjEct for a Research database for ART procedures) included data from cycles recorded between January 2016 and December 2020 in eighteen clinics, providing a robust sample size for Real World Data analyses. Fondazione per la Ricerca Ospedale di Bergamo (FROM), together with expert clinicians in the ART field, promoted the OPERA project with the financial support from two pharmaceutical companies (Merck KGaA, IBSA SA). Participants/materials, setting, methods The Eighteen clinics located in Germany and Italy joining the OPERA data collection, have proven expertise in ART procedures and use MedITEX® DB. The study protocol was reviewed by the competent Ethic Committees and Data Protection Officers. Among the outcomes collected were the mean number of cycles, the pregnancy and birth rate per Embryo Transfer, and the pregnancy and birth rates as a function of female age. The first extraction was scheduled for December 2022. Main results and the role of chance Around 75,000 ART cycles were collected from the first ten participating centers. Among the around 45,000 cycles that have available fertilization information , 11,553 (25.7%) were the In-Vitro Fertilization treatments (IVF), 31,202 (69.3%) Intracytoplasmic Sperm Injection treatments (ICSI), and 2,282 (5.1%) a combination of the two techniques. Of the adopted stimulation protocols, 38.43% (10,538) of the total were with variable antagonists, 31.27% (8,574) were with a single antagonist, 24.31% (6,665) were with a long agonist, 5.51% (1,511) were with a short agonist, and 0.35% (96) were with fixed antagonists. The average number of oocytes retrieved is 11.28, with a median of 10.0. The average number of 2 Pronuclear Oocytes (2PN) obtained is 3.7, with a median of 3.0. Moreover, the average number of 8 cell embryos at day 3 is 2.0, with a median of 2.0. It was also recorded the rate of unsuccessful cycles with no oocytes retrieved (4.8%). Among the cycles collected, 2.9% of the total were from frozen oocytes. Most of the ET (40.0%) were performed 5 days after the oocyte retrieval. Limitations, reasons for caution Amassing ART cycle information does not compensate for the well-known insufficiencies of primary data quality, of information on confounders and of access to patient level data. Moreover, the technical risk of this project is the potential loss of participant confidentiality, mitigated through a full anonymization. Wider implications of the findings The OPERA project may facilitate the transition of ART surveillance from a national aggregate level to a large-scale individual patient and treatment cycle level. Furthermore, as an evolutionary path, the OPERA project may help building large and longitudinal databases, suitable for appropriate epidemiological research in ART. Trial registration number not applicable

P-280 Continuous in-situ monitoring of female hormone levels as a tool to improve the efficacy of assisted reproductive technology (ART) and in-vitro fertilization (IVF) treatment

Abstract Study question Is it possible to remotely monitor a patient’s hormone levels during an ART cycle using an unobtrusive and subcutaneously injectable biosensor for real-time monitoring? Summary answer It is possible for in-situ remote continuous monitoring implantable devices to successfully measure patient blood hormone levels over a clinically relevant concentration range. What is known already Worldwide 48.5 million couples suffer from infertility. In the UK, assisted reproductive treatments (ART) have increased by almost ten-fold in the last 20 years. Hormonal imbalances are the leading cause of female infertility and the success rate of ART tremendously depends on the accurate measurement of the levels of hormones, namely Luteinizing Hormone, Progesterone and Beta Estradiol. These hormone levels change and pulsate during each patient cycle, requiring women undergoing ART treatments to have a blood draw and endocrinology analysis every 2-3 days, making ART treatment highly invasive to a patient’s lifestyle and at a high cost. Study design, size, duration In order to determine the feasibility and potential of the study question, a minimally invasive biosensor to monitor ART hormone levels in real time was developed. The biosensor was tested in vitro for the range of 1 pg/ml to 1 µg/ml in three analytical replicates. The resulting sensitivity of testing was measured in order to evaluate real-work applications. Participants/materials, setting, methods A gold working electrode was utilized and activated using cyclic voltammetry. After activation, a self-assembled monolayer (Thiol-EDC-NHS), was formed on the gold surface, followed by the separate addition of anti-Progesterone4 and Beta-estradiol antibodies. After the addition of each layer, the Differential Pulse Voltammetry (DPV) of the gold electrode was measured. Based on the peak current, calibration curves were plotted and the sensitivity of the sensors was calculated. All electrochemical measurements were performed using CHI potentiostat. Main results and the role of chance This electrochemical hormone biosensor technology) is based on the detection of Progesterone4 and Beta-estradiol biosensor electrodes which can continuously detect hormone levels with a limit of detection (LOD) and limit of quantification (LOQ) of 2.01 and 6.72 pg/ml, respectively. Further to this, the biosensor covers the detection of a wide range of hormone concentrations in the blood from 1 pg/ml to 1 µg/ml. The sensor was also characterised by microscopy techniques such as scanning electron microscope (SEM) and Raman microscopy. Next, the biosensors will be validated in-vivo by conducting animal trials allowing for the main parameters of the biosensors to be optimized according to the in-vivo study. Limitations, reasons for caution This novel implantable biosensor technology requires more upcoming validation in animal models before then being tested clinically to order to assess its ability for widespread use. Wider implications of the findings The development and implementation of an unobtrusive remote and continuous monitoring implantable system for hormonal concentrations monitoring that are vital for success in an ART procedure could transform the entirety of the process as well as positively influence patient's access to care. Trial registration number NA

P-755 Timeless importance of the embryo transfer technique: a real-life retrospective study comparing direct versus afterload catheters

Abstract Study question Can the embryo transfer (ET) technique influence clinical pregnancy rate (CPR)? Summary answer Our study demonstrated that CPR is significantly affected by the ET technique. In particular, with the afterload technique both CPR and easy transfer rates increased. What is known already Despite it having widely demonstrated that the occurrence of difficult ETs reduces the success of assisted reproductive technology (ART) cycles and that afterload technique has showed a decrease in the number of difficult transfers compared to the direct one, few data are available assessing pregnancy outcomes in the two different techniques. The present study represents the progression of a published prospective randomized controlled trial (RCT) performed in the same setting on a smaller population comparing direct and afterload techniques on the difficult transfer rate, but not designed to demonstrate differences in terms of CPR. Study design, size, duration Single center retrospective cohort analysis of 8,189 fresh and frozen single blastocyst transfers performed between January 2016 and December 2021 in a tertiary University affiliated fertility center. Of the total, 2,000 ETs were performed with the direct technique and 6,189 with the afterload one. All fresh single day-5 and single day-5 and day-6 frozen blastocyst transfers performed during the study timeframe were included. Participants/materials, setting, methods Direct technique was the only one used from January 2016 to September 2017. In the clinical trial recruitment period, the choice was given by randomization. From April 2019, only the afterload technique was used: the operator never had chance to choose the technique. Preimplantation genetic testing cycles, gamete donation and day-7 blastocyst transfers were excluded. CPR was the primary outcome, while difficult transfer rate the secondary one. Univariate and multivariate logistic regression have been performed. Main results and the role of chance During the period, 8,189 single blastocyst transfers were performed. Afterload ET showed a percentage of difficult transfers which was almost one third compared to that of the direct ET, being respectively 9.06% and 26.85% (OR 0.27, 95% CI 0.24-0.31p &amp;lt;0.001). Overall, the CPR between the two groups was significantly different: 44.69% in afterload ET and 41.65% in direct ET (OR 1.13, 95% CI 1.02-1.25, p = 0.017). As for the interaction between the two techniques and difficult transfer on CPR, only the direct difficult ET resulted in a significantly lower CPR with an OR of 0.62 (95%CI 0.49-0.77, p &amp;lt; 0.001). Lastly, among the 15 operators that performed the ETs, a range of difficult transfers from 3.8% to 45.4 % in the direct group and 0.8% to 20.5% in the afterload group was found (p &amp;lt; 0.001). Limitations, reasons for caution The main limitations of the study are the difference in sample sizes between the two groups, the wide range of time considered, and the 15 operators included. A further possible reason is the high prevalence of difficult transfer, probably due to the broad definition we used. Wider implications of the findings The study points out how in embryo transfers the use of the afterload technique instead of the direct one significantly improves clinical pregnancy rate and easy transfer rate. Since there is a limited knowledge on the embryo transfer technique impact, our findings aim to increase the effectiveness of embryo transfers. Trial registration number NCT05364528.

O-087 Patient-centric, machine learning (ML)-based personalised prognostics supports fertility specialists to improve access to assisted reproductive technology (ART) and increase overall live birth (LB) outcomes

Abstract Study question Does the use of patient-centric, ML-prognostics counselling report (Univfy® PreIVF Report) affect assisted reproductive technology (ART) conversion (first ART cycle usage) and LB rate (LBR)? Summary answer The use of patient-centric, ML-prognostics counselling report (Univfy® PreIVF Report) by fertility specialists is associated with higher ART conversion and LBR among new patients. What is known already ART is a highly effective and safe treatment for clinical infertility. However, ART remains vastly underutilised resulting in missed opportunities to help more people build families. Commonly used age-based trends often do not address patients' perceived risks including their own ART success probability and ART cost burden as related to their personalised LB probabilities. We previously reported the use of artificial intelligence (AI)/ML to generate patient-centric counselling reports based on ART success prediction models developed and validated for each fertility centre to address their local patient populations in ways that are personalised, relevant and actionable. Study design, size, duration Retrospective cohort analysis. Eight fertility centres from 22 locations across 9 states (US) and Ontario, Canada contributed to the research design, compilation of outcomes data, and interpretation of results. Five centres provided ART utilisation and outcomes data for 15,289 new patients seen in each centre's study period when the Univfy® PreIVF Report was available and data were submitted for aggregated research analysis. Each centre provided 4-6 years of data within the period 2016-2022. Participants/materials, setting, methods The effect of Univfy or No-Univfy Group on ART conversion was analyzed by Chi square tests using aggregated data and separately for each centre's data, for 3 timed analyses, 180-Day, 360-Day and “Ever” (no restriction) after new patient visit. Patients who received the Univfy® PreIVF Report prior to IUI or ART conversion, or had no such conversion after receiving it were placed into the Univfy Group. The No-Univfy Group comprises patients who did not receive a report. Main results and the role of chance Univfy report usage was associated with higher conversions to Direct-ART (by 2.6-, 2.4-, 1.9-folds) and Any-ART (by 2.9-, 3.0-, 2.4-folds) in the aggregated data when analyzed for 180-Day, 360-Day and Ever, respectively; p-value &amp;lt; 0.001. Direct-ART is ART conversion without prior IUI(s); Any-ART conversion includes ART conversion with or without prior IUI(s). In the centre-specific analyses, the fold increase in Direct-ART and Any-ART conversions ranged from 1.8 to 4.5 and 2.2 to 4.7, respectively, in the 360-Day period; p-value &amp;lt;0.001. Univfy® PreIVF Report usage was associated with an increase in estimated LBR ranging from 2.1 to 1.3 folds for the Univfy Group compared to No-Univfy Group (360-Day analysis, p &amp;lt; 0.001) based on conservative versus liberal scenarios. Similar ART conversion and LBR results were observed for 180-Day and Ever analyses, p &amp;lt; 0.001. We used conservative to liberal assumptions for IUI-LBR and NC-LBR because IUI and NC outcomes were not readily available. (Conservative: IUI-LBR 15%, natural conception (NC)-LBR 5%; Liberal: IUI-LBR 25%, NC-LBR 20%). Estimated LBR for ART used clinical ongoing pregnancies and documented live births as LBs and the following LBR assumptions: freeze-all with no transfers yet (50%); gestational carrier ART (45%); ART with unknown outcomes (0%). Limitations, reasons for caution This study was not prospective or randomised. The intended report usage was to support physicians when counselling patients. Although we observed comparable report and ART usage across predicted ART-LB probabilities, there is potential unintentional bias towards higher report or ART utilisation among patients with more favorable clinical characteristics. Wider implications of the findings These results represent our retrospective experience in diverse geographies in North America. We endeavor to collaborate with additional centres to test the reproducibility of AI/ML-driven, validated personalized IVF prognostics on improved overall live birth outcomes and ART access when counselling patients about treatment options. Trial registration number not applicable

P-328 Endometrial receptivity in women with endometriosis undergoing Assisted Reproductive Technology (ART) after frozen embryo transfer: a matched pair case-control study

Abstract Study question Does endometriosis affect endometrial receptivity in frozen/thawed embryo transfer (FET) cycles? Summary answer Stage III/IV endometriosis-patients undergoing ART submitted to FET cycles have implantation, pregnancy and live-birth rates, as well as pregnancy outcomes, similar to control women. What is known already The increased infertility rate observed in women with endometriosis is supposed to be linked, among other factors, to molecular alterations already documented in the endometrial tissue of these affected women. These alterations might influence the interaction between the embryo and the endometrium, leading to a compromised implantation; however, data from the literature are controversial and do not always corroborate the hypothesis of a lower implantation rate in women with endometriosis. Study design, size, duration This is a retrospective matched case-control study including 101 women diagnosed with stage III/IV endometriosis. They were matched in a 1:1 ratio with patients undergoing frozen embryo transfers after ART treatments for other infertility-related indications at the Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico di Milano, between 2015 and 2022. Participants/materials, setting, methods Patients (n = 202) were submitted to ovarian stimulation according to standard protocols and only single embryo transfer cases and the 1st ART cycle with freeze-all protocol were included. To match, it was considered the women's age ( ± 1 year), and the number ( = ) and quality ( ± 1 top vs low) of blastocysts obtained in each cycle, considering the Istanbul consensus as the embryo standard assessment protocol. The main outcome evaluated in this study was implantation rate. Main results and the role of chance Baseline characteristics did not significantly vary between the two study groups, except for AMH levels, which was considerably lower in the endometriosis group compared to control (4.0 [2.7 - 5.4] vs 4.6 [3.7 - 6.5], respectively; p = 0.03). Considering the treatment outcomes, the number of oocytes inseminated/injected in each cycle was similar between endometriosis and control group (8 [7 - 10] vs 9 [7 - 11], respectively; p = 0.26). In line with the matching performed, the number of blastocysts generated did not differ between women with and without endometriosis (3 [2 - 4] vs 3 [2 - 4], respectively; p = 1.00), as well as the number of top-quality blastocysts (2 [1 - 3] vs 2 [1 - 3], respectively; p = 0.76). In regard to our main outcome evaluated, implantation rate in women with endometriosis and their controls were similar (36% vs 40%, respectively; p = 0.52). There was also no difference between the endometriosis group and controls considering cumulative pregnancy outcomes, such as pregnancy rate (58% vs 65%, respectively; p = 0.39), cumulative live birth rate (51% vs 59%, respectively; p = 0.26), pregnancy complications (6% vs 14%, respectively; p = 0.34), and pregnancy loss (16% vs 19%, respectively; p = 0.70). Limitations, reasons for caution As it is a retrospective study, our reports might be subjected to misclassification bias. Also, some of the women in the control group may have asymptomatic undiagnosed endometriosis; however, considering the incidence of this disease, it should not compromise our evaluation. Wider implications of the findings Our present findings give support to the idea that endometriosis does not influence the implantation rate in women with endometriosis undergoing ART submitted to FET. Considering fertility, this finding raises doubts about the clinical relevance of the molecular aberrations detected in the endometrium of women affected by endometriosis. Trial registration number not applicable