Towards a more sustainable balance between optimal live birth rate and supernumerary embryos in ART treatments.

PURPOSE: To assess the relation between number of inseminated oocytes and cumulative live birth rate (CLBR) in order to provide guidance for limiting the number of surplus blastocysts. METHODS: The study was a retrospective, single-center cohort analysis of 1223 ART complete cycles. Cycles were stratified according to female age (≤ 34, 35-38, and 39-42 years) and number of inseminated oocytes (1-5, 6-10, and > 10). Inclusion criteria were indication for IVF/ICSI with own spermatozoa and blastocyst culture up to day 6 of all embryos. RESULTS: In patients younger than 35 years, insemination of more than ten oocytes produced an increase in overall blastocyst number, CLBR (40.3%, 54.3%, and 75.8%, respectively, for each oocyte group) and surplus embryo rate (12.9%, 27.8%, and 49.7% of cases for each group). Instead, in the middle age group, the use of more than ten oocytes was solely associated with an increase in the rate of surplus embryos (1.25%, 21.33%, and 28.68% of cases after stratification for oocyte number). In older patients, neither CLBR (9.1%, 23.9%, and 24.7%, respectively) nor rate of surplus embryos (2.0%, 7.1%, and 13.4% of cases for each group) were higher in cycles with more than ten inseminated oocytes. CONCLUSION: In women up to 38 years, sustainable CLBR are achieved while limiting the number of inseminated oocytes and the resulting blastocysts remaining unused. Based on this notion, novel treatment strategies could pursue high outcome rates, while alleviating the problems derived from surplus stored embryos.

Clinical and laboratory key performance indicators in IVF: A consensus between the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) and the Italian Society of Embryology, Reproduction and Research (SIERR).

PURPOSE: Infertility is increasing worldwide, and many couples seek IVF. Clinical management and laboratory work are fundamental in the IVF journey. Therefore, the definition of reliable key performance indicators (KPIs) based on clinical and laboratory parameters, is essential for internal quality control (IQC). Laboratory performance indicators have been identified and a first attempt to also determine clinical ones has been recently published. However, more detailed indicators are required. METHODS: An Italian group of experts in Reproductive Medicine from both public and private clinics on behalf of SIFES-MR and SIERR was established to define IVF indicators to monitor clinical performance. RESULTS: The working group built a consensus on a list of KPIs, performance indicators (PIs) and recommendation indicators (RIs). When deemed necessary, the reference population was stratified by woman age, response to ovarian stimulation and adoption of preimplantation genetic testing for aneuploidies (PGT-A). Each indicator was scored with a value from 1 to 5 and a weighted average formula - considering all the suggested parameters-was defined. This formula generates a center performance score, indicating low, average, good, or excellent performance. CONCLUSION: This study is intended to provide KPIs, PIs and RIs that encompass several essential aspects of a modern IVF clinic, including quality control and constant monitoring of clinical and embryological features. These indicators could be used to assess the quality of each center with the aim of improving efficacy and efficiency in IVF.

Fine-tuning IVF laboratory key performance indicators of the Vienna consensus according to female age.

PURPOSE: To test the validity of the Vienna consensus laboratory key performance indicators (KPIs) to monitor the outcome of treatments involving women of different age ranges. METHODS: The retrospective cohort study included 862 complete IVF/ICSI cycles carried out between January 2014 and May 2021. All embryos of each cycle cohort were subject to extended culture. The overall population was divided into two groups according to female age: the Vienna consensus (≤ 39 years) and older female age (≥ 40 years). We compared outcomes of a selection of the Vienna performance indicators (PIs) and KPIs, with a focus on measures relevant to embryo cleavage and blastocyst formation. A possible association between total good blastocyst development rate (TGBDR) and cumulative clinical pregnancy rate (CPR) was also assessed. RESULTS: No differences were observed in fertilization and embryo cleavage KPIs between the Vienna consensus and the older female age group (standard IVF fertilization, 67.2 vs. 67.3; ICSI fertilization, 72.3 vs. 75.3; day 2 development, 57.6% vs 58.7%; day 3 development, 52.4% vs. 50.7%, respectively). TGBDR was lower in the older female age group (45.5% vs. 33.4% p < 0.001). Multivariate logistic regression analysis indicated female age as a factor independently associated with TGBDR. Clinical outcomes significantly decreased with increasing female age. CONCLUSION: The study suggests that, while most laboratory outcome measures are reliably applicable irrespective of female age, KPIs describing extended embryo culture should be fine-tuned in consideration of older female age.

The actual impact of SARS-CoV-2/COVID-19 pandemic on IVF activity: a survey across Italian ART centers.

PURPOSE: Since the end of February 2020, SARS-CoV-2 dramatically spread in Italy. To ensure that most of National Health System (NHS) resources were employed to control the pandemic, non-urgent medical procedures (including IVF) were suspended in March 2020. Here, we aimed at assessing the impact of the restrictive measures on Italian IVF activity. METHODS: In May 2020, the Italian ART Register launched an online survey (multiple choices and open answers) across ART centers (89.0% response rate; N = 170/191) to investigate how they were facing the emergency and estimate the reduction in their activity. In February 2022, the official data of the whole 2020 were published and retrospectively analyzed. The ART cycles conducted in Italy in 2020 (67,928 by 57,423 patients) were then compared to those conducted in 2019 (82,476 by 67,633 patients). The estimates formulated through the survey were compared to the actual reduction. RESULTS: In 2020, 14,548 less IVF cycles were conducted with respect to 2019 (- 17.6% reduction). This led to 2539 fewer live births (- 19.8%) than 2019. If the reduction unveiled by the survey launched in May 2020 (i.e., - 35%) would have persisted throughout 2020, a significantly larger impact was expected (4200 less newborns). Instead, the activity was gradually recovered, and it compensated the months of greatest emergency, thus fulfilling the most optimistic scenario. CONCLUSIONS: Italy suffers from the lowest birth rate in Europe, and COVID-19 impact on IVF-derived live births testified how key ART is for Italian demographics. The government should support access to these treatments with dedicated actions.

Monozygotic twin rate among ART centers: a multicenter analysis of data from 18 Italian units.

PURPOSE: The risk of monozygotic twins (MZTs) is increased in couples undergoing assisted reproductive technology (ART) treatments. Several systematic reviews have investigated the possible determinants linked to ART, but results obtained have not been conclusive. The study aims to investigate whether the incidence of MZT differed among ART centers. METHODS: This is a multicenter retrospective cohort study using the Italian ART National Registry database and involving the centers reporting data from individual ART cycles from 2015 to 2019. To investigate the incidence of MZT, only single embryo transfer cycles were considered. Women who had sex-discordant deliveries were excluded. MZT rate was calculated as the number of multiple pregnancies (more than one gestational sac at first ultrasound) out of the total number of clinical pregnancies. A binomial distribution model was used to determine the 95% CI of the frequency of MZT. RESULTS: Eighteen centers were included, and they provided data on 10,433 pregnancies. The total number of MZT was 162, corresponding to an incidence of 1.5% (95% CI: 1.3-1.8%). The rate of MZT among centers varied between 0% (95% CI: 0.0-25.9%) and 3.2% (95% CI: 1.3-8.1%). All the 95% CIs included 1.5%, rejecting the hypothesis that the MZT rate may significantly differ among centers. CONCLUSIONS: The rate of MZT did not significantly vary among ART centers. Local factors are unlikely to explain the increased rate of MZT in ART pregnancies.

ART results with frozen oocytes: data from the Italian ART registry (2005-2013).

PURPOSE: This study is a retrospective collection of aggregated data from all the Italian ART centers reporting to the Italian National Register from cycles started between January 2005 and December 2013. METHODS: Data from both slow freezing (SF) and vitrification (V) were assessed for the period 2007-2013, while during the years 2005-2006 cryopreservation was exclusively performed by SF. RESULTS: In the study period, a total of 2,526,024 oocytes were retrieved (from 378,543 retrievals), of which 1,346,061 (53.3 %) were inseminated in fresh cycles and 214,481 (8.5 %) were cryopreserved. Cryopreserved oocytes were used in 24,173 cycles yielding 19,453 transfer cycles (80.5 % of the thawing/warming cycles) and 3043 clinical pregnancies (15.6 % per transfer). A significant difference in implantation (8.7 vs 12.9 % OR 1.30 CI 1.20-1.40) and pregnancy rates per transfer (12.2 vs 14.9 % OR 1.34 CI 1.23-1.46) was found between SF and V. Complete outcome data was available for 2708 pregnancies (89.8 %), leading to 1882 deliveries and 2152 live births. Neonatal major congenital anomalies were 0.9 % (20/2152). CONCLUSIONS: A wide variation in pregnancy rates were found among different centers and lower rates were reported in donor cycles and in centers with more experience.

Medically assisted reproduction in Italy, 2020 data from the Italian MAR Register.

BACKGROUND: The Italian Medically Assisted Reproduction (MAR) Register (ItMARR) was established by the Decree of the Minister of Health issued on October 7th, 2005. ItMARR has a crucial role in clearly and publicly disseminating epidemiological information on the MAR activities and outcomes. METHODS: ItMARR data is collected in aggregate form and is mandatory as set out in Law 40/2004. The aim of this article is to make a snapshot of the authorized centers that perform IUI and ART in Italy. Data used in this article refer to MAR treatments started between January 1st and December 31st, 2020. RESULTS: MAR techniques were performed by 332 centers. In total, 67,927 ART cycles and 12,171 IUI cycles were performed in 2020. Gametes donation cycles represent 12.9% of ART activity and 4.0% of IUI. ART cycles performed per million women of childbearing age was 6525. In 2020, 2.5% of births in the general population in Italy were a result of application of ART techniques. MAR activity in 2020, has been heavily reduced by the limitations to reproductive treatment due to SARS-CoV-2 pandemic. Pregnancy rates per transfers were 26.7% with fresh techniques, 32.6% with FER, 25.7% with FO, 38.0% with OD and 39.1% with SD. There were fewer multiple deliveries than the previous year. CONCLUSIONS: The ItMARR, has become a great asset in the reproductive health scenario promoting a better MAR information dissemination. ItMARR is working on the implementation towards a "cycle-by-cycle" data collection system. This will bring the Italian monitoring system in line with others European countries.

Fertilization rate as a novel indicator for cumulative live birth rate: a multicenter retrospective cohort study of 9,394 complete in vitro fertilization cycles.

OBJECTIVE: To appraise the fertilization rate as a predictive factor for cumulative live birth rate (CLBR). DESIGN: Multicenter retrospective cohort study. SETTING: Ten in vitro fertilization clinics, whose data were collected and processed by the assisted reproductive technology (ART) Italian National Registry. PATIENT(S): 7,968 couples undergoing 9,394 complete intracytoplasmic sperm injection cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome measure was the CLBR in association with the fertilization rate intervals (<65%-group 1; 65%-80%-group 2; and >80%-group 3). Further data stratification was performed on the basis of maternal age (<34, 35-38, and 39-42 years) and number of retrieved oocytes (5-7, 8-10, and > 10 oocytes). RESULT(S): The CLBR was progressively higher in relation to the fertilization rate in groups 1, 2, and 3 (20.1%, 34.7%, and 41.3%, respectively). The number of recovered oocytes, embryo number per cycle, and cumulative pregnancy rate followed the same trend. The decrease in CLBR with increasing maternal age was significantly correlated with the fertilization rate and CLBR in all 3 maternal age groups. Multivariate logistic regression analysis showed fertilization rate as a factor independently associated with CLBR. CONCLUSION(S): The present data indicated a positive association between the fertilization rate and the CLBR, suggesting the predictive clinical relevance of this parameter and its adoption as a key performance indicator.

Human oocyte cryopreservation with slow freezing versus vitrification. Results from the National Italian Registry data, 2007-2011.

OBJECTIVE: To compare mature human oocytes cryopreservation with slow freezing (SF) and vitrification (VT) in infertile couples. DESIGN: Retrospective study of national Italian data submitted during the period 2007-2011. SETTING: National ART registry. PATIENT(S): Infertile patients with supernumerary oocytes. INTERVENTION(S): Thawing or warming of cryopreserved oocytes and ICSI. MAIN OUTCOME MEASURE(S): oocyte survival, fertilization, implantation and clinical pregnancy rate between SF and VT. RESULT(S): A total of 14,328 cycles with 11,599 transfers, 1,850 pregnancies, 1,168 deliveries and 1,342 babies born were analyzed from 146 reporting centers (range of cycles 1-1,255 per center). The SF oocytes' survival rate was lower than in VT (51.1% vs. 63.1%). Fertilization rate was significantly higher in SF than in VT (SF 71.6% vs. VT 70.1%). VT showed a significantly higher pregnancy rate, both per started cycle (14.4% vs. 12.0%) and per transfer (18.0% vs. 14.8%), and implantation rate (9.5% vs. 8.1%) than SF. However, the range and median pregnancy rate per started cycle were, respectively, 0%-50% and 7.7% in SF and 0%-100% and 6.7% in VT. CONCLUSION(S): VT showed a statistically significant higher performance than SF. As with other ART procedures, the results are not homogeneous among clinics and protocols, but the confirm the clinical value of oocyte cryopreservation in infertile patients.