Characterization of infertile couples and outcomes of their first in vitro fertilization cycle at public fertility centers in Northern and Central Portugal: a five-year cohort study.

Infertility is a worldwide health care issue, affecting approximately one in every six couples, with important psychological, economic, demographic and medical implications ( Feichtinger et al ., 2016 ; Michau et al ., 2019 ). The causes of infertility include male and female-related factors, such as: ovulatory disorders (age or non-age related), Fallopian tube abnormalities, endometriosis, uterine abnormalities and cervical factor. A considerable proportion of infertile couples remain without a diagnosis ( Vaegter et al ., 2017 ). Some causes of infertility are easily identifiable, such as: azoospermia, longstanding oligo/amenorrhea, and bilateral tubal obstruction. However, the situation is less clear in some couples. The uncertain relationship between a test anomaly and the actual cause of infertility makes it difficult to estimate the relative frequency of its causes ( Hull et al ., 1985 ; Vaegter et al ., 2017 ). The assisted reproductive techniques (ART) are the solution for many causes of infertility and several factors can affect the pregnancy rate in a couple. According to the literature there are some pretreatment patients variables that can predict the success of infertility treatment such as: female age, body mass index (BMI), ethnicity, ovarian reserve markers [anti-Müllerian hormone (AMH) and antral follicle count (AFC)], tobacco use, cause of infertility and duration of infertility ( McQueen et al ., 2015 ; Dhillon et al ., 2016 ; Luke, 2017 ). For instance, pregnancy rates decrease significantly with women’s aging whereas anovulatory infertility seems to be associated with good outcomes ( Vaegter et al ., 2017 ). Regarding BMI, and since the incidence of obesity is continually rising, an increasing number of overweight and obese women are seeking fertility treatments. The global impact of obesity on ART is conflicting. Some studies report a decreased embryo quality in obese women, with decreased live birth rates and increased miscarriage rates. However, the majority of studies did not show a significant effect regarding this issue ( Ozekinci et al ., 2015 ; Wang et al ., 2016 ; Luke, 2017 ). It has been shown that tobacco use is associated with reproductive impairments in a dose-dependent manner, namely, diminished ovarian reserve and/or response, reduced uterine receptivity, and adverse pregnancy outcomes ( Dechanet et al ., 2011 ; Zhang et al ., 2018 ). Concerning the male partner, some studies have provided no evidence that advancing age, elevated BMI, and abnormal sperm parameters significantly affect ART success or obstetric outcomes ( Wang et al . 2016 ; Vaegter et al ., 2017 ; Capelouto et al ., 2018 ). There is a lack of data regarding the infertile couple’s characteristics and ART outcomes in the Portuguese population, which motivated the conduction of this multicenter study. The primary objective of the NORCE-INF 14-18 study, conducted in the Northern and Central Regions, was to evaluate the impact of couple characteristics and in vitro fertilization (IVF) cycle parameters on the success rates of the initial IVF treatment among infertile couples seeking assistance at public infertility centers between the years 2014 and 2018. The secondary objectives of this study were to characterize infertile couples initiating treatment at public infertility centers who are undergoing their first IVF cycle, as well as to analyze the outcomes and complications associated with this initial IVF cycle. Furthermore, the study aimed to assess the obstetric outcomes associated with these couples.

A total of 5,250 infertile couples met the inclusion criteria ( Table 1 ). The mean age of female participants was 34.3 years, which exhibited an increase of 5.4 months from 2014 to 2018 (34.1 vs . 34.6; p =0.001). Table 2 illustrates a decline in the proportion of heterosexual couples with a female partner under 31 years of age, alongside an increase in couples with a female partner over 38 years. The majority of couples identified as Caucasian (female: 97.7%; male: 98.1%) and non-smokers (non-smokers: female 79.1%, male 62.1%; smokers: female 15.5%, male 29.4%). The mean BMI for females was 23.7 kg/m 2 , with 33.8% categorized as overweight or obese. The mean BMI for males was 26.08 kg/m 2 , with 61.5% classified as overweight or obese. The average duration of infertility was 45.9 months (range: 0-180 months), translating to a median duration of 3.8 years (0-15 years). Primary infertility was reported in 93.3% of cases, with male factor infertility identified as the most prevalent cause, occurring in 31.3% of cases in isolation and in 51.9% of cases when female-related factors were included. The majority of ovarian stimulation protocols implemented in the analyzed sample were of the short type utilizing gonadotropin-releasing hormone (GnRH) antagonists, accounting for 81.2% of cases. Among these, nearly 68% employed recombinant drugs, 15% utilized highly purified human menotropin (HP-HMG), and approximately 17% utilized a combination of both formulations. The mean dosage of total medication administered was 2,009 International Units (IU), with a minimum of 75 IU and a maximum of 9,750 IU. In nearly 45% of IVF cycles, the number of oocytes retrieved during the pickup ranged from 4 to 9, while 12% of patients were classified as high responders, yielding more than 15 oocytes. There were 97 instances (1.8%) where no viable oocytes were retrieved. The mean number of oocytes retrieved was 8.6, with an average of 7.2 fertilized or injected oocytes and a mean of 3.8 embryos obtained. Detailed cycle characteristics are summarized in Tables 3 and 4 . The GnRH agonist protocol was employed in varying percentages of cycles, ranging from 18.2% in 2015 to 11.6% in 2017 ( p =0.03), while natural cycles accounted for a negligible number (1-5 per year). The use of agonist protocols was least prevalent among couples with male factor infertility (10% of these cycles) and most frequent in couples where the female partner had a diagnosis of endometriosis (55% of these cycles; p <0.001) ( Figure 1 ). Figure 1 Drug protocol used by year of treatment. Throughout the cohort period, no statistically significant differences were observed in the number of oocytes retrieved. However, significant differences were noted in the number of embryos produced (higher in 2016, p =0.01), as well as in the number of embryos cryopreserved, which exhibited a growing trend and peaked in 2018 ( p <0.001). The analysis also revealed significant differences in subsequent FET cycles (p <0.001). Figure 2 illustrates the observed trend towards an increase in “freeze-all” cycles and a decrease in fresh-only transfers, alongside a rise in combined freeze and fresh transfers ( p <0.001). Figure 2 Type of embryo transfer over the studied period. The usage patterns of intracytoplasmic sperm injection (ICSI), classical IVF, and mixed cycles exhibited significant changes over the years, specifically indicating a trend towards a reduction in the utilization of ICSI ( p =0.013) ( Figure 3 ). Figure 3 IVF type. A total of 3,767 cycles involving fresh embryo transfer were recorded, comprising 2,239 double embryo transfers (DET), 1,515 single embryo transfers (SET), and 12 triple embryo transfers (TET). eSET was conducted in 429 cycles, representing 11% of all fresh transfers. Table 5 delineates the distribution of SET, DET, and TET cycles, both with and without the inclusion of frozen embryos. The majority of embryo transfers (50.5%) occurred on day 3, followed by 24.8% on day 5. The distribution of cycles according to transfer day is also presented in Table 6 . Among the cohort, there were 1,483 couples (28.4%) who did not undergo a fresh embryo transfer. Of these, 1,067 cycles (20.3%) were attributed to the absence of transferable embryos, while 416 cycles were categorized as “freeze all” cycles. The mean number of oocytes retrieved in the “freeze all” cycles was 16.6, with a range of 1 to 35. These “freeze all” cycles constituted 10% of the 4,183 cycles with transferable embryos and represented 7.9% of the overall cycles. In terms of complications, there were 22 reported cases (0.4%), which included 19 instances of moderate to severe ovarian hyperstimulation syndrome (OHSS) and three cases of pelvic inflammatory disease. The mean number of oocytes retrieved in the cases of OHSS was 21, with a range varying from 5 to 35 oocytes. Of the OHSS cases, “freeze all” was practiced in 13 instances. In summary, the analysis encompassed 5,250 cycles, which subsequently resulted in 1,372 cryopreservation cycles. During the cohort study period, a total of 1,355 clinical pregnancies were recorded in fresh cycles. Among these, 1,108 were classified as singleton pregnancies (81.8%), while 247 were multiple pregnancies (18.2%), which included three cases of triplets. Miscarriage occurred in 230 clinical pregnancies (17%), encompassing losses in both the first and second trimesters. Additionally, there were 13 terminations of pregnancy (TOP), of which five were due to chromosomal abnormalities (two cases of trisomy 21, one case of trisomy 18, one case of triploidy, and one case of Turner syndrome). Three terminations were attributed to premature rupture of membranes prior to viability, and one was due to intestinal obstruction. The diagnoses or causes of the remaining four TOP cases were not documented. Among singleton pregnancies, there were four instances of intrauterine fetal death, and one twin in a pair experienced intrauterine fetal demise at 23 weeks of gestation, with the surviving twin being delivered at 30 weeks of gestation. Furthermore, the study recorded 16 ectopic pregnancies (1.37%) as well as one heterotopic pregnancy (0.085%) resulting from fresh embryo transfer cycles. The mean gestational age at delivery for pregnancies resulting from fresh cycles was 37.5 weeks, with a median of 38 weeks and a range from 22 weeks to 43 weeks. Prematurity rates noted included 0.8% of infants born before 28 weeks (9 out of 1,110), 3% born between 28 and 31 weeks (33 out of 1,110), and 19.4% born between 32 and 37 weeks (216 out of 1,110). Data on gestational age were missing for six cases (6 out of 1,116). The overall prematurity rate was calculated to be 23.2%, with rates of 12.5% for singleton pregnancies and 70.7% for multiple pregnancies. Specifically, prematurity rates were 2.4% for births occurring before 28 weeks, 7.8% for those between 28 and 31 weeks, and 60.5% for births between 32 and 36 weeks. Regarding the mode of delivery in fresh cycles, 51.8% of deliveries were vaginal, and 48.2% were via cesarean section, with data missing for 3.7% of the deliveries. Pregnancy rates are detailed in Table 7 . The CPR per transfer was 35.9%, encompassing a total of 1,355 cases, while the multiple pregnancy rate per clinical pregnancy was observed at 18.2%, amounting to 247 cases. The LBR per transfer in fresh cycles was calculated to be 29.5%, corresponding to 1,112 live births out of 3,767 transfers. This total includes various pregnancy outcomes, including singleton, multiple, and triplet pregnancies, resulting in an aggregate of 1,321 live newborns. For eSET, the live birth rate was determined to be 35.4%, with a statistically significant variation based on the day of transfer. The LBR ranged from 23% for transfers on Day 3 (D3) to 47% for transfers on Day 5 (D5) ( p =0.001; Table 8 ). Among the 5,250 cycles analyzed, 1,372 yielded at least one frozen embryo, and 1,246 FET cycles were subsequently identified through February 2020. The proportion of FET cycles increased over time, rising from 6.1% in 2014 to 27% of the total cohort in 2018. The number of embryos transferred significantly decreased from 2014 to 2018, indicating a trend towards single embryo transfer ( p <0.001). Furthermore, a shift in the timing of embryo transfer was observed, with Day 5 (D5) transfers increasing from 19% in 2014 to 52% in 2019, while Day 3 (D3) transfers decreased from 46% to 25% during the same period ( p <0.001; Table 9 ). Within the 1,246 FET cycles, 116 (9.3%) did not result in a viable embryo for transfer post-thawing. The CPR per transfer was 30.2%; however, among these clinically confirmed pregnancies, the proportion of miscarriages was 29.9%, which included five late miscarriages. Additionally, there were two cases of medical termination of pregnancy due to trisomy 13 and trisomy 18, as well as five ectopic pregnancies. More than one-fifth (20.6%) of couples with at least one frozen embryo achieved a successful pregnancy that culminated in labor, resulting in a live birth rate per transfer of 21.1%. The multiple pregnancy rate per clinical pregnancy was 14.8% with a multiple live birth rate of 16.1% (38 multiple births out of 236 live births, including one case of triplets). Among the 1,246 cryo-cycles examined, 559 (44%) were classified as natural or modified natural cycles, while 672 (53.9%) were categorized as artificial cycles. Natural cycles exhibited a higher live birth rate and a lower miscarriage rate compared to artificial cycles (22.6% vs . 20.1% and 22.4% vs . 33.7%, respectively), though these differences were not statistically significant. The CPR between natural and artificial cycles were comparable (29.2% vs . 30.9%). The number of embryos transferred per cycle and the timing of the embryo transfer were similar between the two groups. Regarding obstetric outcomes, the median gestational age at birth for singleton pregnancies was 38 weeks (ranging from a minimum of 24 weeks to a maximum of 41 weeks), while for multiple pregnancies, it was 36 weeks (ranging from 26 to 38 weeks) with statistical significance ( p <0.001). The rate of prematurity was 13.9% for singletons and 53.8% for multiples. The overall cesarean delivery rate among FET pregnancies was 58%. Data on the type of labor (spontaneous versus induced) are not available. Additionally, no neonatal outcome data were collected in this analysis. Among all cases included in the study, 78.6% underwent at least one embryo transfer, whether fresh or frozen, with 66.2% receiving a single embryo transfer and 9% receiving two embryo transfers. Within this population, 71.8% of patients underwent a fresh embryo transfer, while 16.6% had at least one FET. The cumulative clinical pregnancy rate (CCPR) per cycle following oocyte retrieval was determined to be 32.6%, accompanied by a CLBR of 25.5%, resulting in a total of 1,601 live newborns. These rates reflect only the first occurrence of pregnancy and live birth for each couple. A subset of 45 couples experienced two pregnancies, while 2 couples had three pregnancies. Notably, 10 couples achieved two live births. The probability of achieving at least one live birth varied across the years, peaking in 2016 at 28.9% and reaching a low of 22.8% in 2015 ( p =0.11; Figure 4 ). This trend corresponds with the probability of at least one clinical pregnancy, which was highest in 2016 at 35.4% and lowest in 2015 and 2018, both at 30% ( p =0.028). Figure 4 Observed cumulative live birth rate (CLBR) by year of treatment. The live birth rate associated with fresh transfer cycles exhibited a significant decline following a plateau at approximately 15 retrieved oocytes ( p <0.001; Figure 5 ). Figure 5 Live birth rate on fresh embryo transfer by number of oocytes. In contrast, the cumulative pregnancy rate and live birth rate per cycle demonstrated no such inflection, with cumulative rates continuing to increase across the entire range of oocyte collection ( p <0.001; Figures 6 and 7 ). Figure 6 Cumulative clinical pregnancy rates (CCPR) by number of oocytes. Figure 7 Cumulative live birth rates (CLBR) by number of oocytes. Additionally, no statistically significant differences were identified concerning prematurity or gestational age at birth when comparing singleton live births resulting from frozen and fresh transfer cycles ( Figure 8 ). Figure 8 Percentage of gestational age at live birth by fresh/frozen embryo transfer (FET) in singletons. A logistic regression model was developed to assess the probability of achieving at least one live birth, incorporating variables identified in the literature as associated with the success of IVF cycles ( Dhillon et al ., 2016 ). The model underwent iterative optimization for stability and relevance, as detailed in Table 10 . The regression equation is expressed as follows: logOR = 2.637 -0,287*(obese(1))-0,115*(age in years)-0,003*(inf duration in months)+0,005*(age*oocyte number)-0,174*(unexpl. Infert(1))-0,105*(smoker or previous smoker(1)) Using this model, an individual who is 27 years old, of normal weight, a non-smoker, with 10 oocytes retrieved, a duration of infertility of 20 months, and no unexplained infertility factor would have an estimated probability of live birth ( OR OR + 1 ) of approximately 38%. Conversely, a 37-year-old individual who is a smoker, obese, has unexplained infertility, and the same retrieval of 10 oocytes over 20 months would demonstrate a significantly lower probability of live birth at approximately 15%.

The rise in the incidence of IVF treatments necessitates enhanced rigor in monitoring these procedures. The systematic implementation of organized databases facilitates optimized data collection, thereby advancing knowledge and surveillance of the treatments administered. Underreporting of adverse events may contribute to an overestimation of the safety of these interventions, as indicated by the latest findings from the European IVF Monitoring Consortium (EIM), underscoring the importance of systematic data collection ( De Geyter et al ., 2020 ). Such data will enable a deeper understanding of national performance outcomes in IVF.

This inaugural collaborative project aims to inspire additional colleagues and centers to consolidate their efforts towards the understanding and enhancement of ART in Portugal. While the data presented herein is valuable, the significance of collaboration in prospective projects and clinical trials may prove to be even greater.

This study encompasses several limitations. It is a retrospective analysis contingent upon the accuracy of the medical records from individual centers. Although a high degree of consistency was achieved in data extraction, issues remain, including missing data and incorrect classifications. It is plausible that some couples may have previously undergone IVF treatment at other public or private centers; however, this potential overlap is unlikely to significantly affect the findings. The male factor had a significant statistical impact, nevertheless, the limitations of this study include the absence of detailed information on specific male factors in the Portuguese national ART registry platform. This multicenter study includes all public centers in Northern and Central Portugal, making it, to the best of current knowledge, the largest investigation to date involving infertile couples undergoing IVF in Portugal, and the only one to calculate cumulative outcomes relative to this population. Of particular significance within this cohort of ART treatments is the steady increase in the age of women undergoing their first IVF treatment over the years. This trend aligns with the increasing average age of women at the birth of their first child, as documented in the literature ( Matthews & Hamilton, 2009 ). Such an increase may raise the probability of infertility and delay diagnosis, subsequently diminishing the chances of successful ART outcomes. Female age remains the principal determinant of IVF success, both in the published literature ( Adebayo et al ., 2023 ) and in current data. Notably, analysis shows a statistically significant increase in female age across the examined periods (2014-2016/2017/2018; 2015-2017/2018; 2016-2018). Additionally, a statistically significant rise in the proportion of women over 38 years old and a decrease in the proportion of women under 31 years old were observed. Among the population studied, a high prevalence of overweight and obesity was noted, with rates of 33.8% for females and 61.5% for males. Female obesity has been associated with a negative independent impact on cumulative IVF success ( Sermondade et al ., 2019 ), as demonstrated in logistic regression analysis. The predominant causes of infertility identified were male factors, both in isolation and in conjunction with female factors (31.3% and 51.9%, respectively), followed by female-related causes, particularly ovulatory and anatomical factors. The prevalence of endometriosis (5.4%) may be underestimated, as broad diagnostic categories could lead to misclassification; endometriosis may co-occur with other male or female factors that might have been classified as mixed causes. In our study, male factor infertility was identified as a significant contributor to the overall infertility experienced by couples when combined with female factors, which highlights the need for targeted interventions that address these prevalent conditions. Future research should focus on understanding the underlying causes of male infertility, as these insights could lead to improved counseling and treatment strategies ( Brincat et al ., 2015 ). Moreover, this aligns with some studies that suggest that addressing male factors in the ART process could enhance overall success rates ( Simon et al ., 2014 ; Jimbo et al ., 2022 ). Despite the effectiveness of both GnRH agonist and antagonist protocols in suppressing premature luteinizing hormone (LH) surges through reversible blockade of pituitary gonadotropin secretion, the precise impact of these protocols on clinical outcomes in IVF and embryo transfer (IVF-ET) remains a topic of debate ( Lai et al ., 2013 ). Nevertheless, GnRH antagonists are clearly associated with reduced rates of OHSS ( Pundir et al ., 2012 ). Current findings also reflect a global trend towards the increased utilization of short antagonist protocols in ART cycles without adversely affecting pregnancy rates ( Siristatidis et al ., 2025 ). Statistical analysis revealed significant annual variations in the use of agonist protocols; however, no clear trend emerged as usage declined steadily from 2015 to 2017 before rising again in 2018. This fluctuation may be attributable to the growing preference for agonist protocols among patients with low ovarian reserve, where the aforementioned OHSS risk is less pertinent. The participating centers exhibited minimal application of natural cycles, consistent with existing literature ( Siristatidis et al. , 2025 ). Half of the couples undergoing their first IVF cycle were able to retrieve six or more mature oocytes and produce three or more embryos. However, only 26% of the total cohort had frozen embryos, although this figure is on the rise, with one-third of couples in 2018 having at least one cryopreserved embryo, and 12.5% resulting from freeze-all cycles. The overall use of ICSI exhibited a slight decline. Reported complications appear to be underestimated, with a rate of only 0.4%. Although the implementation of strategies such as “freeze-all” may lead to lower incidence rates of complications, including OHSS-which is notably underreported-especially given that 12.5% of cryopreserved embryos originated from freeze-all cycles. Over two-thirds of couples (71.8%) underwent fresh transfers during their first IVF cycle. The remaining cases, which did not include embryo transfers, comprised instances where no viable embryos were available or cases designated as freeze-all. The observed high rate of cesarean deliveries (48.2%) in fresh cycles may be attributed to the elevated incidence of multiple gestations and the associated obstetric risks. In terms of FET cycles, nearly a quarter (23.7%) of couples following an IVF/ICSI cycle initiated at least one FET cycle. This notable rate indicates improvement in cryopreservation technologies and represents an additional opportunity for couples to achieve pregnancy, thereby enhancing cumulative probabilities of successful live birth outcomes. Despite higher LBR and lower miscarriage rates favoring natural cycles, the differences were not statistically significant, consistent with existing literature ( Lathi et al. , 2015 ). The live birth rate per transfer was recorded at 21.1%, which, while commendable, indicates potential for further enhancement, given a multiple birth rate of 16.1% that exceeded expectations. It is anticipated that the trend towards eSET may contribute to a reduction in multiple births in both current and future contexts. As observed in fresh transfer cycles, the cesarean delivery rate among FET was also high at 58%, attributable to the increased prevalence of multiple births and their associated risks. Unfortunately, data regarding mode of labor (spontaneous versus induced) were not available, which would provide further insights into these outcomes. The obstetric outcomes surrounding prematurity, especially in multiple pregnancies, warrant concern. While neonatal outcome data were lacking, the high rates of prematurity noted (also in fresh transfer cycles) and their associated complications necessitate careful consideration of the number of embryos transferred. Approximately 26% of couples entering a public IVF program achieved a live birth following their first treatment. This outcome is likely influenced by couple-specific characteristics, and the denominator used includes couples lacking oocytes or transferable embryos. It is plausible that the live birth rate is underestimated as some FET cycles were not appropriately matched to their corresponding IVF cycles (leading to exclusion from the dataset), while others are still in progress or have yet to yield results at the time of data collection. Such factors may also partially account for 2018 being one of the years with the lowest CLBR. The selection of a denominator that includes couples without oocytes or embryos reflects a more accurate assessment of results. The data corroborate findings from the often-cited study by Sunkara et al . (2011) , which associates oocyte quantity with success in fresh transfers, indicating that retrievals exceeding approximately 15 oocytes may correlate with poorer outcomes ( Sunkara et al ., 2011 ). Nonetheless, CCPR and CLBR exhibited continued improvement with increased oocyte retrieval, despite the potential for compromised outcomes in fresh transfers within groups achieving higher retrievals. This observation may elucidate the notable dip in the CLBR depicted in the chart for the 20-24 oocyte retrieval group, which experienced fresh transfer attempts in over 120 cycles. The regression analysis established a robust association between demographic factors and CLBR, confirming that female age is the most significant predictor of ART success, demonstrating an inverse relationship with pregnancy and live birth rates across cycles. The only variable in the model lacking statistical significance was “smoking,” which exhibited inconsistent behavior in the analysis, suggesting either inadequate data collection or high heterogeneity. The binary categorization of smoking status (smoker, former smoker, non-smoker) fails to adequately capture its impact on fertility. Nevertheless, its inclusion remains warranted given its documented significance in prior studies and its biological plausibility ( Marston et al ., 2014 ). A similar issue pertains to the categorization of infertility diagnoses, which presents challenges due to inherent heterogeneity within groups-except for those classified as having “no factors identified.” Logistic regression models provide a fundamental understanding of the probability of success expected for specific couples undergoing their first treatment cycle. Given the diverse nature of infertility, these insights should assist in counseling couples and managing expectations while remaining cognizant of the variability inherent in IVF outcomes. The dataset presents instances such as a live birth resulting from the retrieval of two oocytes from a 39-year-old woman, alongside cases where six 30-year-old women, each having retrieved 15 oocytes, necessitated a second IVF cycle. Despite the low occurrence of these “outlier” percentages, it is crucial to recognize the influence of stochastic variability in these outcomes.

An observational, longitudinal, retrospective cohort study was conducted utilizing data from infertile couples undergoing their first IVF treatment at six public fertility centers in Northern and Central Portugal: Centro Materno- Infantil do Norte (CMIN) - Centro Hospitalar Universitário de Santo António (CHUdSA), Hospital Senhora da Oliveira (HSO) - Guimarães, Centro Hospitalar Universitário de São João (CHUSJ), Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/E), Centro Hospitalar e Universitário de Coimbra (CHUC), and Centro Hospitalar Universitário Cova da Beira (CHUCB), covering the period from January 2014 to December 2018. Inclusion criteria consisted of infertile couples who underwent their first IVF cycle at these ART centers, with oocyte retrieval performed between January 2014 and December 2018. Exclusion criteria included canceled treatments prior to oocyte retrieval; cycles utilizing donated gametes; cycles involving vitrified oocytes; cycles conducted for preimplantation genetic testing and embryo selection; cycles with missing or erroneous mandatory data; and fertility preservation cycles. The primary data source for this study consisted of the local databases routinely employed in each participating center for ongoing treatments. Data extraction was fully anonymized for statistical analysis, employing a unique random identifier for each cycle or couple. This study adhered to applicable legal and regulatory requirements, as well as established research practices, and received approval from the Independent Ethics Committee (IEC) of each participating center. Due to the non-interventional nature of the study, the reliance on data collected in accordance with routine practice, the anonymized analysis, and the presentation of results in aggregate form (with no identifiable patient information), a waiver for obtaining Informed Consent Forms was granted by all IECs. The objective of this study is to analyze the influence of couple and IVF cycle characteristics on the success of the first IVF treatment among infertile couples attending public infertility centers between 2014 and 2018. To achieve this primary objective, the analysis focuses on the effects of factors such as age, tobacco use, BMI, duration of infertility, the number of oocytes retrieved, and the day of embryo transfer on the success of the initial IVF treatment. Success is defined in terms of the cumulative live birth rate (CLBR) among infertile couples. In this context, live birth is characterized as any birth event resulting in at least one live-born infant weighing more than 500 grams and gestating for more than 22 weeks. The primary endpoint of this study is to measure the CLBR, adopting a conservative approach, where each oocyte retrieval cycle represents a single event, and outcomes from any type of embryo transfer associated with that retrieval are considered [fresh embryo transfer and frozen embryo transfer (FET)]. This gives us the global probability of success for a couple reaching oocyte pickup. The denominator does not exclude 0 oocytes and/or 0 transfers: The live birth rate (LBR) per transfer and per transferred embryo was also calculated as follows: Clinical pregnancy was defined as a clinically identifiable gestational sac (with or without embryo). The clinical pregnancy rate (CPR) corresponds to the number of cycles with clinical pregnancy over the total number of cycles. Miscarriage was defined as fetal loss before 22 weeks (154 days) or fetal weight less than 500 grams. Miscarriage was divided into early (≤12 completed weeks from day of oocyte pickup plus 14 days) and late (≥13 weeks). Miscarriage rate is the proportion of women with a spontaneous fetal loss before 22 weeks among those women with a clinical intrauterine gestation. Calculation was done by: Miscarriage rate will be also decomposed by fresh/frozen transfers: Multiple pregnancies rate was calculated dividing clinically identifiable multiple embryos per clinical pregnancy, transfer and oocyte pickup: Multiple birth was defined as the delivery of two or more newborns at or after 22 weeks (154 days) of gestation: Gestational age is given in weeks (w). Cut Offs will be preterm (<37w), very preterm (<32w) and extremely preterm (<28w). eSET is defined as a fertility treatment strategy wherein a single viable embryo is transferred from a cohort of multiple embryos, where at least one additional embryo of similar or superior quality would be suitable for subsequent cryopreservation and potential transfer in a subsequent cycle. The pregnancy rate after eSET was calculated by the ratio of the number of cycles with clinical pregnancy after eSET over the total number of cycles where eSET was performed. The pregnancy rate after 2 embryos transfer was calculated by the ratio of the number of cycles with clinical pregnancy after transfer of 2 embryos over the total number of cycles where transfer of 2 embryos was performed. The proportion of initial IVF cycles resulting in transferable embryos that were not subjected to a fresh transfer was assessed. Data analysis was conducted using IBM SPSS version 26. For the comparison of parametric data, Student’s t-test and analysis of variance (ANOVA) were employed, while the Kruskal-Wallis test was utilized for the analysis of non-parametric data. Distributions and variances were assessed to determine the appropriate statistical tests. Pearson’s Chi-Square test and Fisher’s exact test were applied for the analysis of categorical data. Additionally, binary logistic regression was performed using the Enter method for model building.