{"paper_id":"fcaaa3d7-6887-4940-bb6c-68bdcfe23e8a","body_text":"Thousands of studies have tried to identify individual factors that could interfere\nwith the success rate of In Vitro Fertilization (IVF) treatments, from preparation\nbefore stimulation to follow-up after the embryo transfer (ET). One of the most\ncritical moments in fertility treatment is embryo transfer, which must be performed\nper specific management and follow-up guidelines. The guidelines of the ASRM\n(American Society of Reproductive Medicine) state that the literature for improving\npregnancy rates supports the following interventions: abdominal ultrasound guidance\nfor embryo transfer; removal of cervical mucus; use of soft embryo transfer\ncatheters; placement of embryo transfer tip in the upper or middle (central) area of\nthe uterine cavity, more than 1 cm from the fundus, for embryo expulsion; immediate\nambulation once embryo transfer is completed ( Practice Committee of the American Society for Reproductive Medicine,\n2017 ).\nIn a globalized world, medical tourism has grown more substantial, and many patients\ntravel to clinics in other countries to undergo fertility treatment ( Cohen, 2014 ;  Lunt & Carrera, 2010 ). Sometimes, patients must fly to the\ndestination before and after treatment. This reality affects patients seeking\ndifferent types of medical treatment ( Bergmann,\n2011 ;  Salama  et al .,\n2018 ). The question is whether air travel affects implantation after an\nembryo transfer.\nModern airplanes fly faster and at higher altitudes ( Savona-Ventura & Mahmood, 2022 ). The cabin must be pressurized to\nallow passengers to travel in such conditions. Different mechanisms for\npressurization were created, all involving changes to cabin pressure. Other risks\nassociated with air travel include decreased humidity and radiation exposure ( Savona-Ventura & Mahmood, 2022 ). Flying is\nsafe for clinically pregnant patients ( American\nCollege of Obstetricians and Gynecologists, 2002 ,  Savona-Ventura & Mahmood, 2022 ).\nAlthough recommendations for flying after an embryo transfer abound online, we have\nnot found an indexed study on the subject, but a small one ( Banerjee  et al ., 2017 ). The authors performed a\nretrospective analysis of 100 infertile females who underwent IVF from January 2016\nto June 2016. They were divided into two groups - women who returned to their\ncountries of origin three days after embryo transfer (48 individuals - Group 1) and\nwomen who stayed in the city where the treatment was performed (52 individuals -\nGroup 2). The mean patient age, number of embryos transferred (1,2,3,4), grade (a or\nb), ease of transfer, and endometrial thickness were comparable in both groups. The\npregnancy rate in group 1 was 60.4% (29/48) and 40.4% (21/52) in group 2, with a\n p -value of 0.045.\nAlthough most recommendations indicate that flying is not harmful after an embryo\ntransfer, the scarcity of scientific literature on the subject encouraged our group\nto examine our data for potential correlations.\nThe primary objective of our study is to explore whether post-embryo transfer air\ntravel could impact the outcomes of IVF treatments. Our inquiry aims to provide a\nbetter understanding of this phenomenon and its potential implications for the IVF\ntreatment process.\n\nThis is a single-center, retrospective study performed at a private fertility clinic\n(Originare Medicina Reprodutiva) in São Paulo, Brazil. The data collected\nfrom patient records were anonymized. The study included patients from January 2019\nto March 2022, comprising 2,135 embryo transfers.\nThe study included patients aged 18 to 42 who underwent an embryo transfer (ET) and\nwere divided into two groups according to whether they presumably flew after ET\n(Group 1) or not (Group 2).\nPatients who received donor eggs or embryos were excluded. Positive HCG tests had\nlevels equal to or greater than 5mIU/ml. Embryos rated as ≥3, AA, AB, and BA\nin the Gardner scale were graded as top embryos.\nA low ovarian reserve was defined as an anti-Müllerian hormone (AMH) level\nbelow 1.2 ng/mL, based on the POSEIDON Group’s recommendation ( Poseidon Group, 2016 ), in line with the Bologna Criteria from\nthe ESHRE ( Ferraretti  et al .,\n2011 ). This threshold is similar to other studies referencing AMH cutoffs\nfor successful egg donation ( Oliveira  et\nal ., 2023 ).\nWe classified patients as likely to have flown if they lived more than 400 km from\nthe clinic, implying they likely traveled by plane to return home. In such cases,\nthe clinic did not restrict flying after embryo transfer.\nInitially, the data were described through absolute frequencies and proportions\n(qualitative variables) and measures such as means, standard deviations, minimums,\nmedians, and maximum values (quantitative variables). The Poisson regression model\nwith repeated measures ( Zou, 2004 ) and\ninteractions between location and top embryo rating was used to estimate the crude\nand adjusted Relative Risk. Adjustments were made for age and reason for treatment.\nA log-link function was used to assess the relative risk (RR), and an identity-link\nfunction was used to estimate the average difference in percentage points. All\nanalyses were performed using the SAS 9.4 software. A significance level of 5% was\nadopted.\n\nA total of 2,135 embryo transfers were included in the study. Of these, 1752 were in\ngroup 1 and 383 in group 2. An estimated 17.94% of patients presumably traveled by\nplane after embryo transfer and before the hCG blood test. We analyzed demographic\nvariables, number of embryos transferred, quality of embryos transferred, reason for\ntreatment, and treatment outcomes.\nTables 1 ,  2 , and  3  provide demographic data\nand cycle characteristics. There was no statistical difference between the groups in\nthese variables. On average, patients in group 1 had 1.71 embryos transferred\ncompared to 1.59 in group 2. At least one top embryo was transferred in 22.60% of\nthe procedures performed in group 1  versus  20.97% in group 2. Fresh\ntransfers accounted for 15.53% and 18.54% of the procedures performed in groups 1\nand 2, respectively.\nDemographics for couples seeking treatment.\nCauses for infertility treatment.\nCycle characteristics.\nThe analysis of treatment outcomes is shown in  Tables\n4  and  5 .  Table 4  shows all cycles regardless of the number of embryos\ntransferred and a comparison with similar-grade embryos, categorized as top embryos.\n Table 3  includes the same analysis for\nsingle-embryo transfers (SET) only. We separated SET and transfers with top embryos\nto mitigate confounding factors.\nCycle results with any number of embryos transferred.\nCycle results for single embryo transfers.\nTable 4  shows that group 2 had slightly\nbetter outcomes in pregnancy rate, 61.99%  vs . 62.14%\n( p =0.94). A slight difference was seen in implantation rate,\nfavoring group 2 (38.65  vs . 34.58%  p =0,28). The\nmiscarriage rate was slightly lower in group 1, 28.51%  vs . 32.50%\n( p =0.32), although not significantly. When at least one top\nembryo was transferred, no statistical difference between groups was observed\nregarding pregnancy (71.71%  vs . 70.48%  p =0.69),\nImplantation (46.59%  vs . 43.04%  p =0.64), and\nmiscarriage rates (26.83%  vs . 30.77%  p =0.56).\nTable 5  shows no statistical difference\nbetween groups 1 and 2 in single embryo transfers. Regarding pregnancy rate, the\ndifference was 56.65%  vs . 59.72% ( p =0,33) and\n67.63%  vs . 68.57% ( p =0.85) for top embryos. For\nimplantation, the difference was 45.47%  vs . 51.11%\n( p =0.13) and 53.85  vs . 59.38%\n( p =0.42) for the general and top embryo analysis. Lastly, the\nrelative risk for miscarriage rate was 0.87 ( p =0.59) and 0.87\n( p =0.77) when looking only at top embryos.\n\nThe process of IVF is delicate and complex, involving various stages and\ninterventions designed to optimize the chances of success. One of these key stages\nis the ET, which consists of the transfer of one or more embryos into the uterus of\nthe woman undergoing treatment. The success of an ET depends on a range of factors,\nincluding the health of the embryos, the quality of the uterine lining, and the\ntiming and conditions of the transfer itself. However, other factors could also pose\nchallenges to the success of ET, such as flying on an airplane after the procedure,\na topic that has not been adequately explored.\nMedical tourism has grown to become a multibillion-dollar business ( Cohen, 2014 ;  Lunt & Carrera, 2010 ). Patients seek other places for treatment for\nmany reasons, including cost, quality, and regulatory factors (the possibility of\nselecting gender and performing embryo analysis) ( Bergmann, 2011 ;  Salama  et\nal ., 2018 ). At least 20,000 to 25,000 couples are estimated\nto receive in-vitro fertilization (IVF) care annually in clinics located abroad\n( Peter, 2010 ), not to mention clinics\nwithin their country of origin but outside their home towns.\nGiven the increasing prevalence of air travel for medical treatment, it is essential\nto understand whether flying might pose a risk to patients undergoing IVF. While\nstudies have examined the impact of air travel on fertility more broadly, limited\nresearch has been conducted specifically on the effects of flying after an ET ( dos Santos Silva  et al ., 2009 ;\n Lauria  et al ., 2006 ;\n Mahoney, 2010 ).\nStudies have shown that the embryo can move around after the transfer. The once\ncommon belief that patients must lie down after a transfer has proven pointless\n( Practice Committee of the American Society for\nReproductive Medicine, 2017 ). Patients are generally concerned that\nexternal forces, such as those experienced during a flight, could disrupt the\nimplantation process.\nNewer airplane models are designed to minimize exposure to external factors such as\nradiation and atmospheric pressure changes, which may have previously been a\nconcern. The longest commercial flights expose passengers to no more than 15% of the\nmaximum annual radiation exposure (1mSv) ( Barish,\n2004 ). A 10-hour flight exposes passengers to 0.05mGy, while a chest\nx-ray exposes patients to twice as much radiation. A CT scan exposes patients to\n8-30mGy of radiation ( Savona-Ventura & Mahmood,\n2022 ). When flying over 7,000m, passenger cabin pressure is generally\nmaintained at the equivalent of an altitude of 1,524-2,438 m ( Aerospace Medical Association, 2008 ). At such altitudes,\npassengers experience mild hypoxia, with resting oxygen saturation (SpO2) estimated\nat 90-95%, which is considered safe for healthy individuals ( Silverman & Gendreau, 2009 ).\nAnother potential risk is exposure to whole-body scans used at airports during\nsecurity checks. These scanners use low-energy, low-intensity ionizing radiation\nthat does not penetrate the skin ( Auvinen  et\nal ., 2012 ).\nSeveral papers have analyzed the frequency of spontaneous miscarriages in flight\nattendants, with contradictory results ( Aspholm\n et al ., 1999 ;  Cone\n et al ., 1998 ;  dos\nSantos Silva  et al ., 2009 ;  Freeman  et al ., 2004 ;  Grajewski  et al ., 2015 ;  Lauria  et al ., 2006 ;  Park  et al ., 2017 ). One study showed that\nflight attendants who flew more hours were more likely to have a miscarriage ( Cone  et al ., 1998 ). Although\nfertility problems are more likely in this population, they appear to be linked to\nthe job’s high physical job demands, lack of sleep, and disturbances in the\ncircadian rhythm ( Grajewski  et al .,\n2015 ;  Lauria  et al .,\n2006 ;  Mahoney, 2010 ;  Mills & Kuohung, 2019 ).\nPregnant women are not exposed to greater risk because of flying when compared to\nwomen who did not choose air travel ( Csorba\n et al ., 2019 ;  American College of Obstetricians and Gynecologists, 2002 ;  Savona-Ventura & Mahmood, 2022 ). It is\nworth noting that those women flew significantly less than female flight attendants.\nThe American College of Obstetricians and Gynecologists (ACOG) stated that\noccasional air travel is safe for pregnant women and has recommended measures to\nminimize potential risks ( American College of\nObstetricians and Gynecologists, 2002 ). In their review, the European\nBoard and College of Obstetrics and Gynaecology (EBCOG) did not mention\ncontra-indications to air travel for healthy pregnant women ( Savona-Ventura & Mahmood, 2022 ).\nWhile there is no definitive research on the impact of air travel after ET, the\navailable evidence suggests that it is unlikely to worsen treatment outcomes ( Banerjee  et al ., 2017 ). Our\nstudy also found no effect on ET from air travel.\nAs far as we know, this is the first study published in an indexed journal evaluating\nthe potential impact of air travel after embryo transfer. The main strength of our\nresearch is the significant number of embryo transfer patients from a single center,\nwhich means that the technical protocols for endometrial preparation, embryo\nculture, embryo freezing and thawing, and the embryo transfer technique are similar\nand homogeneous.\nHowever, this study has several limitations. Its retrospective nature is a primary\nweakness, as is the lack of control over whether patients took a flight as intended,\nthe timing of airplane travel after the transfer, flight duration, the presence or\nabsence of layovers, and potential flight difficulties such as turbulence.\nFurthermore, we could not quantify the cumulative birth rate due to the way data was\nextracted, which limits our ability to draw more definitive conclusions about\noverall reproductive success. Lastly, we could not compare the impact of different\nAMH levels across groups, which we understand could impact the results, especially\nin PCOS patients with high AMH levels ( Vale-Fernandes  et al ., 2023 ).\nIt is important to note that further research is needed to confirm our findings.\nWhile evidence suggests that flying after an ET is safe, a prospective study is\nwarranted to determine whether air travel impacts treatment outcomes.\nWe did not find negative impacts of air travel after embryo transfer. Allowing\npatients to return home after this procedure may reduce stress and treatment costs.\nOur data shows that patients should be encouraged to return home, even by\nairplane.\n\nOur study explored whether post-embryo transfer (ET) air travel could impact in vitro\nfertilization (IVF) outcomes. Given the growing prevalence of medical tourism and\nthe need for patients to travel for fertility treatment, it is crucial to understand\nthe potential risks associated with flying after an ET. Our retrospective analysis\nof 2,135 embryo transfers revealed no significant differences in pregnancy,\nimplantation, or miscarriage rates between patients who traveled by airplane after\nET and those who did not. While the study suggests that flying post-ET is generally\nsafe, it is essential to acknowledge its limitations, including its retrospective\nnature and lack of control over flight-related variables. Therefore, further\nresearch, ideally prospective studies, must confirm these findings and provide\ndefinitive guidelines. Based on the available data, we conclude that air travel\nafter ET does not negatively impact IVF treatment outcomes. This finding supports\nthe notion that patients can safely return home by airplane after undergoing an\nembryo transfer, potentially reducing stress and treatment costs.","source_license":"CC-BY-4.0","license_restricted":false}