{"paper_id":"fc1ec1af-12b3-48c2-87c7-70dffb20dde6","body_text":"This is the 32 nd  report of the Latin American Registry of Assisted\nReproduction (RLA), which started in 1990 as the first multinational and regional\nregistry of assisted reproductive technology (ART). Since 2012, reports have been\npublished simultaneously in  Reproductive BioMedicine Online  and\n JBRA Assisted Reproduction , the official journal of the Latin\nAmerican Network of Assisted Reproduction (REDLARA). As in previous years, this\nreport provides information on the utilization, availability, effectiveness, safety\nand perinatal outcomes of ART treatments initiated between 1 January and 31 December\n2020, and babies born up to September 2021. This report provides some additional\ninformation on the relationship between endometriosis in its different forms and the\nclinical outcome of ART procedures.\nART = assisted reproductive technology; FET = autologous frozen embryo transfer; FP =\nfertility preservation; FRESH = initiated fresh autologous IVF/ICSI cycles; FTO =\nembryo transfer cycles with autologous and donated vitrified/warmed oocytes; ICSI =\nintracytoplasmic sperm injection; OD = oocyte donation with fresh or frozen/thawed\nembryos; RLA = Latin American Registry of Assisted Reproduction.\n\nData on ART were collected from 188 centres in 16 countries in Latin America ( Supplementary Table 1 ), covering fresh\nautologous cycles of IVF and intracytoplasmic sperm injection (ICSI);\npreimplantation genetic testing (PGT); frozen embryo transfer (FET) preceded by both\nfresh embryo transfer cycles and from freeze-all cycles; oocyte donation, including\nthe transfer of fresh and frozen/thawed embryos; fertility preservation; and\nvitrified/warmed oocyte cycles (FTO), both autologous and heterologous.\nAll institutions reporting to RLA have been accredited by an independent body within\nREDLARA. The forms used for this process can be accessed on  www.redlara.com  Participating centres agree to have their data\npublished by RLA and so no specific consent forms were requested for the scientific\ndisclosure of data. The method of data collection in 2020 resembles that of previous\nyears ( Zegers-Hochschild  et al .,\n2020 ), making results comparable. The definitions used are those\npublished in the International Glossary on Infertility and Fertility Care ( Zegers-Hochschild  et al .,\n2017 ). When calculating clinical pregnancy or delivery rates per oocyte\nretrieval, cases resulting in total embryo freezing were not included in the\ncalculation.\nIn order to study the relationship between endometriosis and ART outcomes,\nmodifications were introduced in the data collection system. This is the first year\nin which more detailed information on the type of endometriosis was registered,\nincluding additional information on how the diagnosis was reached\n(clinical/ultrasound or surgical), as well as its type and localization (peritoneal,\novarian, deep infiltration) and the type of surgery performed.\nThe cumulative delivery rate was calculated from aspirations and their related fresh\nand frozen transfer cycles taking place between January and December 2020. We\nconsidered the first delivery after the transfer of either fresh or frozen/thawed\nembryos, or both, obtained after a reference oocyte retrieval. Only centres\nproviding a permanent identification number were included in this calculation. In\nthis year, cumulative deliveries were calculated from longitudinal data provided by\n141 institutions in 15 countries. Results are expressed as: (i) cumulative delivery\nrate starting with all fresh transfers; and (ii) cumulative deliveries including\nonly women having surplus frozen embryos apart from their fresh transfers.\nUtilization of ART is expressed as the total number of cycles performed per million\ninhabitants. Considering that not all cycles carried out in every country were\nreported to the RLA, the best possible estimate of the non-reported cycles was\nobtained through information provided by regional directors of REDLARA,\nembryologists, clinicians and industry representatives. The magnitude of the\nestimates, which constitutes a potential source of error, is expressed as degrees of\nconfidence according to  Dyer  et al .\n(2019 ) and later applied by  Zegers-Hochschild  et al . (2021 ).\nFor the purpose of visualizing the influence of women’s age on delivery rate, a\ngeneral equation of the straight line was used to calculate the slope of decrease in\ndelivery rate as age increases.\nTo test for the effect of age, number of embryos transferred and stage of embryo\ndevelopment at transfer on the delivery rate per embryo transfer, Poisson regression\nmodels with robust SE were used when analysing cross-sectional associations. The\nresults are reported as prevalence ratios with their 95% confidence intervals (CI).\nPoisson regression models with robust SE were used because they provide prevalence\nratio estimates that are relatively easy to interpret, rather than odds ratios\n( Grant, 2014 ). Robust SE were used to\ncorrect underinflation when applying the Poisson model for binary outcomes. When\nvariables were not stratified by age, analyses were adjusted for it.\n p <0.05 was considered statistically significant and STATA 17\n(StataCorp LP, College Station, TX, USA) was used to perform all analyses.\n\nA total of 188 centres in 16 countries reported 87,732 initiated cycles during 2020,\nresulting in 12,778 deliveries and 14,405 live births. This represents one more\ncountry than in previous years, following the incorporation of Costa Rica. Overall,\nthere was a drop of eight centres and 19,188 ART cycles, resulting in 8441 fewer\nbabies born. This is largely the result of the transitory and/or definitive closure\nof centres associated with the COVID-19 pandemic. In fact, this is the first time\nthere has been a drop in the number of cycles and centres reporting. Regional trends\nremain unchanged, and Brazil is still the largest contributor with 46.0% of all\ninitiated cycles, followed by Mexico and Argentina with 17.0% and 16.8% of cycles,\nrespectively ( Table 1 ). Fresh-initiated IVF\nand ICSI cycles still predominate with 45% of initiated cycles, followed by 25.8% of\nFET and 15.3% of oocyte donation. As will be seen later in this manuscript, this\nrelatively high proportion of cycles, including reproductive donation, is related to\na high proportion of women ≥40 (34%), compared with only 18% in Europe in\n2018 ( European IVF Monitoring Consortium,\n2022 ) and approximately 26% in the USA, as reported by SART in 2022\n( https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?reportingYear=2020 ).\nTreatment with art reported in Latin America, 2020.\nGiven that not all initiated cycles are intended to result in an immediate pregnancy,\nand not all oocytes collected can be fertilized or the resulting embryos\ntransferred, pregnancy rate and delivery rate are directly affected by how selective\nthe denominator is. In order to understand and interpret the outcome under different\ntreatment modalities,  Figure 1  provides the\nsequence of events that need to be considered when looking at the outcome with a\nspecific technique (IVF/ICSI, oocyte donation, FET), starting with: initiated cycle;\ncancellations before follicle aspiration; aspirations with or without mature\noocytes; freeze-all oocytes, embryos, or both; the number of cycles with fertilized\noocytes or failed fertilization; and the number of cycles with viable embryos for\ntransfer or normal embryos after PGT. After all these events have been considered\nand adjusted for, pregnancy and delivery rates can be calculated with a\nwell-established denominator: initiated, aspirated and transfer cycles. This\ndetailed description, however, is only possible in a cycle-based data collection\nsystem.\nFigure 1 Events that affect the outcome of fresh IVF and ICSI (IVF/ICSI), fresh\nand frozen oocyte donation and autologous frozen embryo transfer in\nLatin America, 2020. FET=frozen embryo transfer; FRESH=initiated fresh\nautologous IVF/ICSI cycles; OD=oocyte donation; PGT=preimplantation\ngenetic testing (PGT-A, PGT-M, PGT-SR reported together).\nEvents that affect the outcome of fresh IVF and ICSI (IVF/ICSI), fresh\nand frozen oocyte donation and autologous frozen embryo transfer in\nLatin America, 2020. FET=frozen embryo transfer; FRESH=initiated fresh\nautologous IVF/ICSI cycles; OD=oocyte donation; PGT=preimplantation\ngenetic testing (PGT-A, PGT-M, PGT-SR reported together).\nAs seen in  Figure 2 , the RLA collects data\non a vast proportion of ART cycles carried out in most countries in the region;\nin particular, it covers between 74% and 94% of the major contributors. Overall,\nUruguay and Argentina, two countries with laws providing universal care to ART,\nhave the highest utilization, with 558 and 490 cycles per million inhabitants,\nrespectively, followed by Panama, with 425 cycles/million inhabitants. Brazil is\nby far the major contributor in the region, but its utilization is still very\npoor (231 cycles/million population).\nFigure 2 Use of assisted reproductive technology (ART). Estimated number of\ninitiated cycles per million inhabitants by country in Latin\nAmerica, 2020. *Rate of reporting = number of cycles reported to the\nregistry / total or estimated total number of cycles performed in\nthe country.\nUse of assisted reproductive technology (ART). Estimated number of\ninitiated cycles per million inhabitants by country in Latin\nAmerica, 2020. *Rate of reporting = number of cycles reported to the\nregistry / total or estimated total number of cycles performed in\nthe country.\nAs seen in  Figure 3 , in the last 7 years,\nthe proportion of women ≤34 has dropped from 31.7% to 24.7%; women\n≥40 have continued to increase, from 27% to 34%. According to this, 75.3%\nof women treated in the region were 35 years or older, with profound variations\namong countries. The proportion of women ≥40 in the major contributors\nwere Brazil 35.3%, Mexico 25.3%, Argentina 41.9% and Peru 40.4% (data not shown\nhere). This is very important when comparing treatment outcomes in different\ncountries and regions. The proportion of women ≥40 is only 18% in Europe\nand approximately 26% in the USA ( European IVF\nMonitoring Consortium, 2022 , and  https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?reportingYear=2020 ,\nrespectively).\nFigure 3 Age distribution of female partner in fresh IVF and intracytoplasmic\nsperm injection (IVF/ICSI) in Latin America, 2014-2020.\nAge distribution of female partner in fresh IVF and intracytoplasmic\nsperm injection (IVF/ICSI) in Latin America, 2014-2020.\nIn 2020, there were 39,418 fresh-initiated IVF/ICSI cycles, but as reported in\n Figure 1 , after discarding cancelled\ncycles, freeze-all cycles and other conditions impeding embryo transfer, the\nnumber of cycles where at least one mature oocyte was collected dropped to\n17,253. Furthermore, after discarding cases with failed fertilization, no embryo\ndevelopment and PGT cases without normal embryos, the number of transfer cycles\nwas further reduced to 11,101.  Table 2 \nprovides clinical pregnancy rates (CPR) and delivery rates per oocyte retrieval\nand embryo transfer according to the age of women and the type of fertilization\nprocess. Consistent with previous years, ICSI represents 84.8% of transfers.\nThis high proportion of ICSI, without a clear explanation apart from the fear of\nfertilization failure, has had small changes over the last decade (85.7% in\n2010;  https://redlara.com/registro.asp ). When stratified by the age of\nthe female partner, the pregnancy rate by oocyte retrieval was significantly\nhigher in IVF than in ICSI only in women ≥35 years\n( p <0.0001). However, there were no differences in the\ndelivery rate by oocyte retrieval and delivery rate by embryo transfer. As\nexpected, the chances of achieving a delivery decreased with age.\nCPR and delivery rate in fresh autologous IVF and ICSI cycles stratified\naccording to the age of women in 2020.\nOf all fresh transfers, SET continued to increase, from 36.2% as reported in 2019\n( Zegers-Hochschild  et al .,\n2022 ), to 38.3% in 2020, and 90.6% of all fresh transfers included a\nmaximum of two embryos ( Figure 4 ). The\neffect of the number of embryos transferred on the CPR, delivery rate and\nmultiple births can be seen in  Figure 4 .\nBoth the CPR and delivery rate after DET were significantly higher than after\nSET (CPR: prevalence ratio 1.36; 95% CI 1.32-1.48;  p <0.001)\n(delivery rate: prevalence ratio 1.35; 95% CI 1.26-1.45;\n p <0.001). However, its impact on multiple births increased\nfrom 1.8% of monozygotic twins (MZT) after SET to 20.9% of twins after DET and\n21.5% after TET.\nFigure 4 Clinical pregnancy rate (CPR), delivery rate (DR) and multiple\ndelivery rate (MDR) per embryo transfer in IVF and ICSI cycles\naccording to the number of embryos transferred in Latin\nAmerica,2020. SET=single-embryo transfer; DET=double-embryo\ntransfer; TET+=triple or more embryo transfer.\nClinical pregnancy rate (CPR), delivery rate (DR) and multiple\ndelivery rate (MDR) per embryo transfer in IVF and ICSI cycles\naccording to the number of embryos transferred in Latin\nAmerica,2020. SET=single-embryo transfer; DET=double-embryo\ntransfer; TET+=triple or more embryo transfer.\nThere were 4252 SET, which were further stratified into eSET (when one embryo is\nchosen from a larger cohort of available embryos) and oSET (when one embryo is\ntransferred because there are no more embryos available for transfer) and eDET\nover oDET (the transfer of only two embryos because there are no more embryos\navailable for transfer). In this universe, eSET represented 39.5% of SET. As\nseen in  Table 3 , both CPR and delivery\nrates were significantly greater after eSET (42.8% and 32.4%, respectively)\ncompared with oSET (18.2% and 11.9%, respectively) ( p  <\n0.0001); and after eDET (50.3% and 35.8%, respectively) compared with oDET\n(30.9% and 20.7%) ( p  < 0.0001). These differences were\naccompanied by an almost three times higher rate of monozygotic twinning after\noSET than eSET. Furthermore, when two embryos were transferred, the rate of\ntwins was also significantly higher in eDET than oDET ( p  <\n0.0001). The higher rate of dizygotic twins after eDET can be considered an\nindirect expression of higher embryo implantation rate associated with better\nembryo quality in women with the capacity to generate more embryos. When this\ncomparison was made after the transfer of only blastocyst ( Supplementary Table 2 ), the delivery rate\nafter the transfer of eDET (37.9%) and eSET (34.2%) were only 3.7% points\ndifferent. However, the rate of multiple births rose from 1% of MZT after\nblastocyst eSET to 30.5% after blastocyst eDET.\nCPR, delivery rate and gestational order in elective and non-elective SET\nand DET in fresh autologous IVF/ICSI in 2020.\nWhen examining the impact of the age of women, and consistent with the 2019\nreport, the delivery rate after transferring eSET was higher than after oSET at\nall ages ( p  = 0.0355 to  p  < 0.0001).\nOverall there was no significant difference in delivery rate of eDET compared\nwith eSET (prevalence ratio 1.16; 95% CI 0.97-1.38;  p =0.103).\nIn women between 35 and 40 years, delivery rates of eDET were higher than eSET\nbut the differences in this group were not statistically significant ( Figure 5 ).\nFigure 5 Delivery rate per embryo transfer (DR/ET) in IVF and ICSI cycles\naccording to the age of the female partner and the number of embryos\ntransferred in Latin America, 2020. eDET=elective double-embryo\ntransfers; eSET=elective single-embryo transfers;\nICSI=intracytoplasmic sperm injection; oSET=transfer of only one\nembryo because there are no more embryos available for transfer.\nDelivery rate per embryo transfer (DR/ET) in IVF and ICSI cycles\naccording to the age of the female partner and the number of embryos\ntransferred in Latin America, 2020. eDET=elective double-embryo\ntransfers; eSET=elective single-embryo transfers;\nICSI=intracytoplasmic sperm injection; oSET=transfer of only one\nembryo because there are no more embryos available for transfer.\nAs seen in  Figure 1 , there were 13,383\ninitiated cycles representing 15.3% of all cycles performed in the region. After\ndiscarding cancellations, freeze-all cycles and other factors, there were 9581\nembryo transfers. In contrast with autologous reproduction, the delivery rate\nusing donated oocytes was practically unaffected by the age of recipients ( Figure 6 ). Furthermore, delivery rates and\nmiscarriage rates were compared in oocyte recipients and in a selected\npopulation of women ≤34 years with autologous reproduction. To homogenize\nboth populations, only FET cycles were used. In the absence of PGT, the\nmiscarriage rate in oocyte recipients (18.2%) was significantly greater than in\na subset of autologous reproduction in women ≤34 years (14.9%)\n( p =0.002). In the same way, the delivery rate by embryo\ntransfer was significantly lower in oocyte recipients (29.3%) compared with\nwomen ≤34 years (32.7%) ( p <0.001). Furthermore, in a\nsubset of women where PGT was performed, there were no differences in\nmiscarriage rate in oocyte recipients (11.9%) and women ≤34 years with\ntheir own eggs (11.1%). The delivery rates in these two groups (39.6% and 40.9%)\nwere also not significantly different. Therefore, in this very young female\npopulation, the use of PGT significantly reduced the rate of miscarriage and\nincreased delivery rates, both in autologous cycles and in oocyte recipients\n( Table 4 ). When comparing outcomes\naccording to the number of embryos transferred, the CPR, delivery rate and\nmultiple births in 3091 fresh transfers and 6490 frozen/thawed transfers can be\nseen in  Supplementary Tables 3  and  4 .\nEffect of PGT on the delivery rate and miscarriage rate according to age\nof women in autologous FET and OD FET (2020).\nFor miscarriage the denominator is clinical pregnancies; for\ndeliveries, the denominator is embryo transfers.\nLikelihood of having a miscarriage. The reference group is ‘with\nPGT’.\nLikelihood of delivery. The reference group is ‘with PGT’.\nFigure 6 Delivery rate per embryo transfer (DR/ET) in fresh autologous IVF and\nintracytoplasmic sperm injection (ICSI) and fresh oocyte donation\n(OD) cycles according to the age of the female partner in Latin\nAmerica, 2020.\nDelivery rate per embryo transfer (DR/ET) in fresh autologous IVF and\nintracytoplasmic sperm injection (ICSI) and fresh oocyte donation\n(OD) cycles according to the age of the female partner in Latin\nAmerica, 2020.\nThe better outcome after FET was multifactorial, but in this case, it results\nfrom a much higher proportion of blastocyst transfers in FET (19,253/22,178;\n86.8%) compared with fresh transfers (5917/11,101; 53.3%). This finding is\nreassuring because when comparing the outcome after blastocyst transfer in a\nfresh and FET cycle (without PGT), both CPR and delivery rates showed no\nsignificant difference (CPR: prevalence ratio 0.98; 95% CI 0.93-1.02;\n p =0.349; delivery rate: prevalence ratio 1.00; 95% CI\n0.94-1.06;  p =0.964) ( Figure\n8 ). It is thus likely that the better results seen in FET over fresh\ntransfers was a consequence of a much higher proportion of blastocyst transfers\nin the former.\nFigure 8 Clinical pregnancy rate, delivery rate and babies born after fresh\nand frozen-thawed blastocyst transfers in Latin America, 2020.\nFET=frozen embryo transfer; ICSI=intracytoplasmic sperm injection;\nPGT=preimplantation genetic testing.\nClinical pregnancy rate, delivery rate and babies born after fresh\nand frozen-thawed blastocyst transfers in Latin America, 2020.\nFET=frozen embryo transfer; ICSI=intracytoplasmic sperm injection;\nPGT=preimplantation genetic testing.\nDuring 2020 there were 19,142 autologous freeze-all cycles ( Figure 1 ), and a total of 7484 FET resulting from autologous\nfreeze-all procedures performed in 2020 and in previous years. There were 2092\ndeliveries with an overall delivery rate per transfer of 28.0% ( Supplementary Table 6 ). Furthermore, 810\nwomen had more than one transfer from embryos originating from the same\nfreeze-all procedure. The cumulative delivery rate in this subgroup reached\n30.4% in spite of a mean age of 37.5 (5.39) years.\nIn order to compare the outcome of freeze-all cycles and FET cycles resulting\nfrom failed fresh transfers, all cases where PGT was performed were excluded\nfrom the calculation. There were 10,476 autologous FET transfers and 2772\ndeliveries, with a delivery rate of 26.5%, compared with a delivery rate of 28%\nin freeze-all cycles; this is significantly greater ( p =0.0258),\ndemonstrating that when the best embryos are selected for delayed transfer, the\nchances of delivery are even greater than after fresh transfers ( Figure 4 ).\nThe proportion of blastocyst transfers over cleaving embryos increases year after\nyear. It represented 30.3% of all transfers in 2016, increasing to 77.6% in\n2020; and as mentioned before, in cases of FET, it represents 86.8% of all\ntransfers compared with 53.3% in fresh IVF/ICSI. In oocyte donation cycles (both\nfresh and frozen), the proportion of blastocyst transfers reached 74.7%. When\ncomparing the delivery rate and multiple birth rate after the elective transfer\nof 8-cell cleaving embryos (day 3) and elective transfer of day 5 blastocysts in\nIVF and ICSI cycles, the delivery rates were significantly higher after the\ntransfer of blastocysts, both in eSET and eDET (eSET: prevalence ratio 1.69; 95%\nCI 1.27-2.24;  p <0.001; eDET: prevalence ratio 1.23; 95% CI\n1.08-1.39;  p <0.001) ( Figure\n9 ). Furthermore, following eDET the proportion of multiple births was\nalso significantly higher after blastocyst transfer (30.5% compared with day 3\ncleaving embryos [17.9%],  p <0.001).\nFigure 9 Delivery rate (DR) and multiple delivery rate (MDR) per embryo\ntransfer in IVF and ICSI cycles according to eSET and eDET and the\nday of embryo transfer in Latin America, 2020. eDET=elective\ndouble-embryo transfer; eSET=elective single-embryo transfers.\nDelivery rate (DR) and multiple delivery rate (MDR) per embryo\ntransfer in IVF and ICSI cycles according to eSET and eDET and the\nday of embryo transfer in Latin America, 2020. eDET=elective\ndouble-embryo transfer; eSET=elective single-embryo transfers.\nIn the last 5 years, the proportion of aspirations leading to PGT has increased\nalmost 2.5 times in all age categories ( Figure\n10 ). In 2020, a total of 144/188 centres (76.6%) reported 8920\naspirations of autologous fresh cycles where PGT was performed. This corresponds\nto 24.1% of aspirations with at least one mature oocyte. When stratified by age,\nthe percentage of aspirations with PGT was 12.9% in women ≤34, 23.7% in\nwomen 35-39 years and 33.4% in women ≥40 years ( Figure 10 ). Furthermore, there were 5094 embryo transfer\ncycles, of which 4178 transfers were from autologous cycles (82%) and 916 (18%)\nfrom oocyte donation. The mean age of women undergoing autologous PGT was 38.3\n(SD 3.97); and the age distribution included 17.6% in women ≤34 years,\n20.2% in women 35 to 37 years, 19.7% in women 38 and 39 years and 42.5% in women\n≥40 years. In oocyte donation, the mean age of donors was 25.5 (SD\n4.75).\nFigure 10 Five year trends in the use of preimplantation genetic testing (PGT)\nin autologous fresh cycles for aspirations with at least one mature\noocyte in different age groups in Latin America, 2016-2020.\nFive year trends in the use of preimplantation genetic testing (PGT)\nin autologous fresh cycles for aspirations with at least one mature\noocyte in different age groups in Latin America, 2016-2020.\nOverall, there were 27,287 embryos examined. Out of 5114 embryos in women\n≤34 years, the proportion of normal embryos was 50.2%. Out of 11,990\nembryos in women 35-39 years, the proportion of normal embryos was 40.1%. In\nwomen ≥40 years, out of 10,183 embryos, the proportion of normal dropped\nto 22.9%. Furthermore, in 3166 embryos generated from oocyte donors, the\nproportion of normal embryos was 63.9%. The effect of PGT on the delivery rate\nand miscarriage rate can be seen in  Table\n4 . When stratified by age, PGT significantly decreased miscarriage in\nall age categories, including women under 34 years ( p =0.041),\nand oocyte donation ( p =0.002). Concerning the effect of PGT on\nthe probability of achieving birth, the differences in deliveries with and\nwithout PGT are again significantly greater with PGT at all age groups,\nincluding oocyte donation ( p <0.001) ( Table 4 ).\nEndometriosis was present, either as a primary or secondary diagnosis, in 11,153\nout of 39,418 initiated fresh cycles (28.3%). Of these, peritoneal endometriosis\ndiagnosed via laparoscopy comprised 11,040 (99%); there were 45 cases of partial\noophorectomy and either aspiration or removal of endometriotic cysts. There were\nalso 41 cases of surgery for deep infiltrating endometriosis and 24 cases of a\ncombination of these categories. Given that severe endometriosis was reported in\nvery few cases, a comparison was made between the outcome of cases where\nperitoneal endometriosis was managed by laparoscopic surgery and a ‘control\ngroup’ of tubal and endocrine factors excluding premature ovarian insufficiency\n( Supplementary Table 7 ). In this\n‘control group’, cases with a secondary diagnosis of endometriosis were also\nruled out. Similarly, cases included in peritoneal endometriosis did not have\nother associated diagnoses.  Supplementary Table\n7  provides information on the numbers and the mean number of oocytes\ncollected, as well as the delivery rates in these two groups of women,\nstratified by age categories. Although the mean number of oocytes collected in\nwomen ≤34 and ≥40 years was significantly lower in the presence of\nendometriosis (≤34: 9.3 [6.274]  versus  11.6 [7.201]:\n p <0.0001; 95% CI 2.1171-2.4829; ≥40: 5.2 [4.415]\n versus  6.0 [5.327]:  p <0.0001; 95% CI\n0.6363-0.9637), the delivery rate per embryo transfer was 38.3\n versus  33.9 ( p =0.0744; 95% CI -0.4378 to\n9.1025) in the ≤34 years age group and it was significantly greater in\nwomen ≥34 years; 35-39: 31.2  versus  24.1:\n p =0.0004; 95% CI 3.2333 to 10.8003 and ≥40: 16.8\n versus  12.2:  p =0.0353; 95% CI 0.3185 to\n8.3988.\nCumulative delivery rates were calculated in the first cohort of 11,101\naspiration cycles irrespective of whether women had surplus frozen embryos for\ndelayed transfer, and in a subgroup of 4344 women who, apart from their fresh\ntransfers, had supernumerary embryos frozen for further transfers, irrespective\nof whether they were used during 2020. To calculate cumulative deliveries, this\nlatter group is the one that better reflects what cumulative chances are,\nbecause women that do not have frozen embryos had their only chance after the\nfresh transfer. As seen in  Figure 11 , the\ndelivery rate per fresh transfer is notably higher at all ages in women having\nsurplus frozen embryos compared with all women, including a high proportion of\naspirations without surplus embryos (60.9%). As expected, the delta between\nfresh and cumulative outcome was further increased in the selected cohort of\nwomen having frozen embryos for delayed transfer. Another interesting\nobservation in this subcohort of women having fresh and frozen embryos was the\nless pronounced slope of the drop in deliveries as age increases. As seen in\n Figure 11 , the effect of age on the\nchances of delivery was less prominent in women who generated more embryos.\nFigure 11 Cumulative delivery rate (cDR) per aspiration cycle and delivery rate\nper fresh embryo transfer (DR/ET) in IVF and ICSI cycles according\nto the age of the female partner in Latin America, 2020. (a) All\naspirations irrespective of whether there were frozen embryos for\nfurther transfer. (b) Only aspirations with surplus frozen embryos.\nThe equation represented by a dotted line is a reflection of the\nslope of decrease in delivery rate between women of 29 years and\nyounger and women up to 38 years of age.\nCumulative delivery rate (cDR) per aspiration cycle and delivery rate\nper fresh embryo transfer (DR/ET) in IVF and ICSI cycles according\nto the age of the female partner in Latin America, 2020. (a) All\naspirations irrespective of whether there were frozen embryos for\nfurther transfer. (b) Only aspirations with surplus frozen embryos.\nThe equation represented by a dotted line is a reflection of the\nslope of decrease in delivery rate between women of 29 years and\nyounger and women up to 38 years of age.\nCumulative delivery rates reached 48.8% in a subset of 545 women ≤34 years\nwith only one fresh (eSET) and one frozen/thawed blastocyst transferred;\ncompared with 43.5% when two fresh blastocysts were simultaneously transferred\nin 648 women. Furthermore, multiple births increased from 1.6% of MZT in\ncumulative blastocyst SET to 30.5% after a fresh blastocyst DET ( Figure 12 ).\nFigure 12 Delivery rate (DR) and multiple delivery rate (MDR) after the\ntransfer of two fresh elective blastocysts (eDET Bc) or one fresh\nelective blastocyst + 1FET blastocyst (eSET Bc+1FET Bc) in women\nunder 35 years of age in Latin America, 2020.\nDelivery rate (DR) and multiple delivery rate (MDR) after the\ntransfer of two fresh elective blastocysts (eDET Bc) or one fresh\nelective blastocyst + 1FET blastocyst (eSET Bc+1FET Bc) in women\nunder 35 years of age in Latin America, 2020.\nPerinatal mortality (PNM) was calculated from 12,778 deliveries and 14,582\nbirths. Of these, 75.6% of newborns were singletons; 23.6% were twins and 0.9%\ntriplets or more. PNM is consistent with previous years, with 7.7‰ of perinatal\ndeaths in singletons, rising to 24.4‰ in twins and 64.0‰ in triplets and more\n( Table 5 ). On the other hand, preterm\nbirth ( Figure 13 ) took place in 17.2% of\nsingletons, rising to 67.8% in twins and 92.3% in triplets. Of these, extreme\npreterm births (≤33 weeks of gestation) increased from 3.5% in singletons\nto 13.4% and 38.5% in twins and triplets, respectively. The negative impact on\nthe health of mothers and children born from preterm and extreme preterm births\nhas been described in detail by  Sazonova\n et al.  (2013)  and the  Practice Committee of the Society for Reproductive Endocrinology\nand Infertility, Quality Assurance Committee of the Society for Assisted\nReproductive Technology, and the Practice Committee of the American Society\nfor Reproductive Medicine (2022) .\nPerinatal mortality according to gestational order in 2020.\nEarly neonatal deaths are excluded.\nPerinatal mortality = (stillbirth + early neonatal death) / (live\nbirth + stillbirth + early neonatal death).\nFigure 13 Preterm birth and perinatal mortality (PNM) according to order of\ngestation and gestational age in Latin America, 2020.\nPreterm birth and perinatal mortality (PNM) according to order of\ngestation and gestational age in Latin America, 2020.\nIn 2020, there were 22,643 initiated FET cycles, representing 25.8% of all\nprocedures ( Table 1 ) and 66.6% of all\nautologous transfers ( Figure 1 ). This\nrepresents a consistent increment over the past 25 years ( Figure 7 ). In this same time interval, the mean number of\nembryos transferred in fresh cycles dropped from 3.6 in 1996 to 1.6 in 2020\n( Figure 7 ). Of all initiated FET\ncycles, 465 (2.1%) were discontinued. Reasons for discontinuation are described\nin  Figure 1 . Therefore, out of 22,178 FET\ncycles, the overall CPR and delivery rate per transfer were 41.4% and 29.0%,\nrespectively ( Supplementary Table 5 ). The\nhigher CPR and delivery rate in FET compared with fresh transfers are observed\nacross all numbers of embryos transferred ( Figure\n4  and  Supplementary Table 5 ).\nThis better outcome in FET over fresh transfers (delivery rate/transfer 29.0%\nand 23.9%, respectively) is significantly higher at all ages\n( p <0.001). This is also accompanied by a reduction in\nmultiple births. Out of 6423 FET deliveries reported in this period, 88.1% were\nsingletons, 11.7% were twins and 0.2% were triplets and higher ( Supplementary Table 5 ), compared with 85.1%\nof singletons, 14.5% twins and 0.4% triplets and higher after 2661 deliveries in\nfresh autologous transfers (data not shown here). Differences between singletons\nand between twins are highly significant ( p =0.0001 and\n p =0.0002, respectively).\nFigure 7 Proportion of frozen embryo transfer (FET) cycles and the mean number\nof embryos transferred in fresh cycles in Latin America,\n1996-2020.\nProportion of frozen embryo transfer (FET) cycles and the mean number\nof embryos transferred in fresh cycles in Latin America,\n1996-2020.\nA total of 7558 initiated cycles of oocyte vitrification for fertility\npreservation were reported, of which 7204 had at least one mature oocyte\n(95.3%). The age distribution of women has shown minimal changes over recent\nyears and the proportion of women trying to preserve their fertility at\n≥38 years remains very high (44.8%) ( Figure 14 ). As expected, the mean number of vitrified oocytes\ndecreased with age. The mean (SD) numbers of metaphase II vitrified oocytes was\n7.04 (5.83), with ample variations according to women’s age. In women\n≤34, the mean was 9.02 (7.05); in women 35-38 was 7.32 (5.73); 39-40\nyears was 5.77 (4.52) and in women ≥40 was 4.54 (3.76) oocytes. In 95.1%\nof cases, the reason for oocyte vitrification was a postponement of fertility\nfor reasons other than cancer, which represented the primary reason for\nfertility preservation in 4.9% of cases (data not shown here).\nFigure 14 Fertility preservation cycles per year according to the age of women\nin Latin America, 2017-2020. Numbers include only cycles where at\nleast one mature oocyte was collected.\nFertility preservation cycles per year according to the age of women\nin Latin America, 2017-2020. Numbers include only cycles where at\nleast one mature oocyte was collected.\n\nThis is the 32 nd  report on ART procedures performed in Latin America. As a\nresult of the COVID-19 pandemic, the number of new centres reporting to RLA as well\nas the total number of cycles dropped for the first time in three decades. Some\ncentres restricted medically assisted reproduction to non-ART procedures, while\nothers definitely closed. Other centres had to restrict their personnel, making\nreporting more difficult. During this reporting year, one centre from Costa Rica has\nbeen incorporated in REDLARA, after ART was re-established in that country following\nthe ruling by the Inter-American Court of Human Rights in favour of IVF ( http://www.corteidh.or.cr/docs/casos/articulos/seriec_257_esp.pdf ).\nThe best estimate for ART utilization by country is depicted in  Figure 2 . Uruguay and Argentina continue to have the highest\nutilization due to laws providing free access. However, in spite of this, economic\nrestrictions in low or middle income (LMIC) countries limit access to ART for a\nwider population. The mean number of ART cycles per million in 15 Latin American\ncountries (204 cycles/million) is only 14.6% of the mean utilization of 1400 cycles\nper million in 21 European countries with full reporting during 2018 ( European IVF Monitoring Consortium, 2022 ).\nFurthermore, utilization in Uruguay and Argentina is more similar to 638\ncycles/million (excluding fertility preservation) reported by the CDC/USA in 2019\n( https://www.cdc.gov/art/state-specific-surveillance/2019/pdf/State-Specific-ART-Surveillance-U.S.-2019-Data-Brief-h.pdf ).\nThe reason for utilization in a wealthy country like the USA being closer to LMIC in\nLatin America has to do with the type of reproductive policies in the majority of\nstates in the USA and in the Americas altogether, where out-of-pocket funding\nprevails; this is in comparison with state funding or partial or total reimbursement\nin the majority of high-income countries in Europe.\nThe proportion of FET cycles continues to rise, representing 66.6% of all autologous\ntransfers. This has been associated with a continuous drop in the mean number of\nfresh embryos transferred to 1.6.\nAs reported in the past, both pregnancy and delivery rates after FET were higher than\nafter fresh transfers, irrespective of the number of embryos transferred. This might\nlook surprising, considering that a large proportion of FET cycles result from\nfailed fresh transfers. The main reason for this is the proportion of blastocyst\ntransfers, which is much higher in FET (86.3%) compared with only 53.6% after fresh\ntransfers. As seen in  Table 3 , Supplementary\n Table 2  and  Figure 9 , the delivery rate after elective and non-elective SET and DET\nwere significantly higher after blastocyst transfer compared with the transfer of\ncleaving embryos. The beneficial role of blastocyst transfer, rather than the\ntransfer of fresh or frozen embryos, is further examined in  Figure 8 , where both CPR and delivery rates were the same if\nonly blastocysts were transferred in a group of 5867 fresh transfers and 15,169 FET.\nFurthermore, the transfer of embryos after a freeze-all cycle yields better\npregnancy and delivery rates than after regular FET. This is because most, if not\nall, regular FET result from failed fresh transfers where the best embryos have\nalready been used, while in freeze-all cases, the best blastocyst is thawed first.\nAgain, this shows that selection of the best blastocyst for transfer is what yields\nthe best results, either through morphology assessment or after the addition of\nPGT.\nIn 2020, for the first time, collaborating institutions were asked to describe the\ntype of endometriosis when this was part of a primary or secondary diagnosis. This\nincluded how the diagnosis was reached, and when reached surgically (mostly\nlaparoscopic), centres were asked to describe the type of surgery performed,\nclassified into five categories: peritoneal fulguration, cystectomy or drainage of\nendometrioma, deep infiltration, partial oophorectomy and a combination of the\nabove. Endometriosis was diagnosed by direct visualization in 11,153 out of 39,418\ninitiated cycles (28.3%). The number of oocytes collected as well as the delivery\nrate, stratified by age, were compared in 5779 cases of women having peritoneal\nendometriosis as the only diagnosis, excluding freeze-all cycles, compared with\nwomen having tubal and/or endocrine factors, excluding ovarian insufficiency. As\nseen in  Supplementary Table 7 , delivery\nrates were higher in the endometriosis group in all age categories, in spite of\ngenerating fewer oocytes. Therefore, women with a history of peritoneal\nendometriosis fulgurated or removed by laparoscopy seem to have better ART outcomes\nthan women with tubal or endocrine factors. Although we understand that in the\nabsence of a randomized trial the above statement cannot be certified, findings in\nthis database are in agreement with a study by  Opøien  et al . (2011 ) who showed better ART\noutcomes in minimal or mild endometriosis after surgical removal of endometriotic\ntissue; a review by  Senapati  et al. \n(2016) , using the SART database, agreed with the findings here, that in\nthe absence of comorbidity, endometriosis yields fewer oocytes but higher pregnancy\nand delivery rates.\nThe number of centres and cycles reporting PGT is increasing year after year. In\n2020, 76.6% of centres reported PGT, which included 24.1% of aspirations with at\nleast one mature oocyte. PGT was used in 27,287 blastocysts, most of which were\nexamined by next-generation sequencing. The proportion of aneuploidy was 49.8% of\nembryos in women ≤34 years; 59.9% of embryos in women aged 35-39, and 77.1%\nof embryos in women ≥40 years. Furthermore, the proportion of aneuploidy in\n3166 embryos generated from oocyte donors (mean age 25.5 years) was 36.1%. As seen\nin  Table 4 , using PGT decreased miscarriage\nrates and increased delivery rates at all ages, including oocyte recipients.\nFurthermore, when comparing the outcome in oocyte recipients and autologous\nreproduction in women ≤34 years, miscarriage was significantly higher and\ndelivery rates significantly lower in oocyte recipients. Nevertheless, when PGT was\nused, both markers improved and the differences disappeared. There is indeed a\nbenefit in using PGT to achieve higher reproductive efficiency at all ages; however,\nthe question is whether it is cost beneficial at all ages, which will be highly\ndependent on reproductive health funding policies. Irrespective of the wealth of a\ncountry, when the majority of treatments are out-of-pocket funded, most consumers\nbelong to a subgroup of middle or high-income individuals. In this subgroup there is\na triad consisting of families with fewer children, delayed childbearing and a\nprogressive seeking for certainties. With this in mind, the question of absolute\nbenefit of PGT prevails over the balance between costs for the intended benefit.\nThis in part explains the increasing use of technology (PGT) to ensure, as far as\npossible, the birth of healthy children.\nUnlike previous years, this report calculates the cumulative delivery rate from\naspirations taking place only during 2020. In this cohort of 11,101 aspirations,\nonly 4344 (39%) had surplus embryos available for future transfer. Therefore, if\ncumulative births are calculated starting from the whole cohort, the majority of\nwomen (61%) will not have a second chance of a birth resulting from the initial\naspiration cycle. This is most likely due to the high proportion (34%) of women who\nwere aged 40 years and older.\nWhen the cumulative delivery rate was calculated only among women having surplus\nfrozen embryos available for future transfers, the chance of a birth after a fresh\ntransfer was already higher at all ages; the delta generated by the subsequent FET\n(cumulative) was also higher. Furthermore, the negative impact of age on\nreproductive efficiency is less pronounced in women generating more embryos. This is\nwell represented by the slope of the line representing lower chances of a birth as\nage increases, which is less steep in women capable of generating more embryos from\na single aspiration cycle ( Figure 11 ). Another\ninteresting finding is the better outcome after the sequential transfer of two\nblastocysts (1+1) compared with the simultaneous transfer of two blastocysts in\nwomen ≤34 years. Although the differences in delivery rates are not huge, the\nrate of multiple births is almost 20 times higher after the simultaneous transfer of\ntwo blastocysts (1.6% compared with 30.5%, respectively) than after 1+1 ( Figure 12 ). The impact of multiple births in\nterms of perinatal mortality and preterm and extreme preterm births can be seen in\n Table 5  and  Figure 13 . In 2020, 65% of all multiple births resulted from\nwomen ≤34 years and oocyte recipients. Therefore, a strategy of 1+1\nblastocysts in these two groups of women should significantly reduce multiple\nbirths, maintaining acceptable delivery rates.\nTo summarize, after more than 30 years of a south-south multinational cooperation\nprogramme among multiple institutions and countries of Latin America, we believe\nthis to be the most efficient way of procuring regional sustainable growth.\nThroughout the years, numerous centres have acquired the capacity and the ability to\nregister their data in a systematic way, which is a fundamental step towards\nprogress. The software developed by RLA allows every centre to automatically access\nresults of their own data and compare them with the global results of their country\nand sub-region. This has proved to be of immense value when developing strategies to\nprocure a better balance between safety and efficacy, especially with the\ndifficulties that result from a population where 34% of women are aged ≥40\nyears and the majority of treatments are out-of-pocket funded.\nThe data that has been used is confidential.","source_license":"public-domain-us","license_restricted":false}