RESUMO
Importance: Cancer is a leading cause of death among children worldwide. Treatments used for medically assisted reproduction (MAR) are suspected risk factors because of their potential for epigenetic disturbance and associated congenital malformations. Objective: To assess the risk of cancer, overall and by cancer type, among children born after MAR compared with children conceived naturally. Design, Setting, and Participants: For this cohort study, the French National Mother-Child Register (EPI-MERES) was searched for all live births that occurred in France between January 1, 2010, and December 31, 2021 (and followed up until June 30, 2022). The EPI-MERES was built from comprehensive data of the French National Health Data System. Data analysis was performed from December 1, 2021, to June 30, 2023. Exposure: Use of assisted reproduction technologies (ART), such as fresh embryo transfer (ET) or frozen ET (FET), and artificial insemination (AI). Main Outcomes and Measures: The risk of cancer was compared, overall and by cancer type, among children born after fresh ET, FET, or AI and children conceived naturally, using Cox proportional hazards regression models adjusted for maternal and child characteristics at birth. Results: This study included 8â¯526â¯306 children with a mean (SD) age of 6.4 (3.4) years; 51.2% were boys, 96.4% were singletons, 12.1% were small for gestational age at birth, and 3.1% had a congenital malformation. There were 260â¯236 children (3.1%) born after MAR, including 133â¯965 (1.6%) after fresh ET, 66â¯165 (0.8%) after FET, and 60â¯106 (0.7%) after AI. A total of 9256 case patients with cancer were identified over a median follow-up of 6.7 (IQR, 3.7-9.6) years; 165, 57, and 70 were born after fresh ET, FET, and AI, respectively. The overall risk of cancer did not differ between children conceived naturally and those born after fresh ET (hazard ratio [HR], 1.12 [95% CI, 0.96 to 1.31]), FET (HR, 1.02 [95% CI, 0.78 to 1.32]), or AI (HR, 1.09 [95% CI, 0.86 to 1.38]). However, the risk of acute lymphoblastic leukemia was higher among children born after FET (20 case patients; HR 1.61 [95% CI, 1.04 to 2.50]; risk difference [RD], 23.2 [95% CI, 1.5 to 57.0] per million person-years) compared with children conceived naturally. Moreover, among children born between 2010 and 2015, the risk of leukemia was higher among children born after fresh ET (45 case patients; HR, 1.42 [95% CI, 1.06 to 1.92]; adjusted RD, 19.7 [95% CI, 2.8 to 43.2] per million person-years). Conclusions and Relevance: The findings of this cohort study suggest that children born after FET or fresh ET had an increased risk of leukemia compared with children conceived naturally. This risk, although resulting in a limited number of cases, needs to be monitored in view of the continuous increase in the use of ART.
Assuntos
Neoplasias , Técnicas de Reprodução Assistida , Humanos , Feminino , Neoplasias/epidemiologia , Neoplasias/etiologia , Técnicas de Reprodução Assistida/efeitos adversos , Técnicas de Reprodução Assistida/estatística & dados numéricos , Masculino , Criança , França/epidemiologia , Pré-Escolar , Fatores de Risco , Adulto , Gravidez , Estudos de Coortes , Sistema de Registros , Modelos de Riscos Proporcionais , Lactente , Transferência Embrionária/efeitos adversos , Transferência Embrionária/estatística & dados numéricosRESUMO
In this retrospective study conducted at Sichuan Jinxin Xinan Women and Children's Hospital spanning January 2015 to December 2021, our objective was to investigate the impact of embryo cryopreservation duration on outcomes in frozen embryo transfer. Participants, totaling 47,006 cycles, were classified into 3 groups based on cryopreservation duration: ≤1 year (Group 1), 1 to 6 years (Group 2), andâ ≥6 years (Group 3). Employing various statistical analyses, including 1-way ANOVA, Kruskal-Wallis test, chi-square test, and a generalized estimating equation model, we rigorously adjusted for confounding factors. Primary outcomes encompassed clinical pregnancy rate and Live Birth Rate (LBR), while secondary outcomes included biochemical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late miscarriage rates, preterm birth rate, neonatal birth weight, weeks at birth, and newborn sex. Patient distribution across cryopreservation duration groups was as follows: Group 1 (40,461 cycles), Group 2 (6337 cycles), and Group 3 (208 cycles). Postcontrolling for confounding factors, Group 1 exhibited a decreased likelihood of achieving biochemical pregnancy rate, clinical pregnancy rate, and LBR (ORâ <â 1, aORâ <â 1, Pâ <â .05). Furthermore, an elevated incidence of ectopic pregnancy was observed (ORâ >â 1, aORâ >â 1), notably significant after 6 years of freezing time [aORâ =â 4.141, 95% confidence intervals (1.013-16.921), Pâ =â .05]. Cryopreservation exceeding 1 year was associated with an increased risk of early miscarriage and preterm birth (ORâ >â 1, aORâ >â 1). No statistically significant differences were observed in birth weight or sex between groups. However, male infant birth rates were consistently higher than those of female infants across all groups. In conclusion, favorable pregnancy outcomes align with embryo cryopreservation durations within 1 year, while freezing for more than 1 year may diminish clinical pregnancy and LBRs, concurrently elevating the risk of ectopic pregnancy and preterm birth.
Assuntos
Aborto Espontâneo , Gravidez Ectópica , Nascimento Prematuro , Criança , Gravidez , Feminino , Masculino , Recém-Nascido , Humanos , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Peso ao Nascer , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Nascido Vivo , Transferência Embrionária/efeitos adversos , Taxa de Gravidez , Criopreservação , Gravidez Ectópica/epidemiologia , Gravidez Ectópica/etiologiaRESUMO
PURPOSE: In this first of two companion papers, we critically review the evidence recently published in the primary literature, which addresses adverse maternal and neonatal pregnancy outcomes associated with programmed embryo transfer cycles. We next consider whether these pathological pregnancy outcomes might be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation. Finally, in the second companion article, we explore potential etiologies and suggest strategies for prevention. METHODS: Comprehensive review of primary literature. RESULTS: The preponderance of retrospective and prospective observational studies suggests that increased risk for hypertensive disorders of pregnancy (HDP) and preeclampsia in assisted reproduction involving autologous embryo transfer is associated with programmed cycles. For autologous frozen embryo transfer (FET) and singleton live births, the risk of developing HDP and preeclampsia, respectively, was less for true or modified natural and stimulated cycles relative to programmed cycles: OR 0.63 [95% CI (0.57-0.070)] and 0.44 [95% CI (0.40-0.50)]. Though data are limited, the classification of preeclampsia associated with programmed autologous FET was predominantly late-onset or term disease. Other adverse pregnancy outcomes associated with autologous FET, especially programmed cycles, included increased prevalence of large for gestational age infants and macrosomia, as well as higher birth weights. In one large registry study, FET was associated with fetal overgrowth of a symmetrical nature. Postterm birth and placenta accreta not associated with prior cesarean section, uterine surgery, or concurrent placenta previa were also associated with autologous FET, particularly programmed cycles. The heightened risk of these pathologic pregnancy outcomes in programmed autologous FET does not appear to be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation, although the latter may contribute a modest degree of increased risk for fetal overgrowth and perhaps HDP and preeclampsia in FET irrespective of the endometrial preparation. CONCLUSIONS: Programmed autologous FET is associated with an increased risk of several, seemingly diverse, pathologic pregnancy outcomes including HDP, preeclampsia, fetal overgrowth, postterm birth, and placenta accreta. Though the greater risk for preeclampsia specifically associated with programmed autologous FET appears to be well established, further research is needed to substantiate the limited data currently available suggesting that the classification of preeclampsia involved is predominately late-onset or term. If substantiated, then this knowledge could provide insight into placental pathogenesis, which has been proposed to differ between early- and late-onset or term preeclampsia (see companion paper for a discussion of potential mechanisms). If a higher prevalence of preeclampsia with severe features as suggested by some studies is corroborated in future investigations, then the danger to maternal and fetal/neonatal health is considerably greater with severe disease, thus increasing the urgency to find preventative measures. Presupposing significant overlap of these diverse pathologic pregnancy outcomes within subjects who conceive by programmed embryo transfer, there may be common etiologies.
Assuntos
Transferência Embrionária , Pré-Eclâmpsia , Resultado da Gravidez , Humanos , Feminino , Gravidez , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Pré-Eclâmpsia/patologia , Pré-Eclâmpsia/epidemiologia , Recém-Nascido , Fertilização in vitro/efeitos adversos , Fertilização in vitro/métodos , Criopreservação , Hipertensão Induzida pela Gravidez/patologia , Hipertensão Induzida pela Gravidez/epidemiologia , Fatores de RiscoRESUMO
STUDY QUESTION: Is large for gestational age (LGA) observed in babies born after frozen embryo transfer (FET) associated with either the freezing technique or the endometrial preparation protocol? SUMMARY ANSWER: Artificial cycles are associated with a higher risk of LGA, with no difference in rate between the two freezing techniques (vitrification versus slow freezing) or embryo stage (cleaved embryo versus blastocyst). WHAT IS KNOWN ALREADY: Several studies have compared neonatal outcomes after fresh embryo transfer (ET) and FET and shown that FET is associated with improved neonatal outcomes, including reduced risks of preterm birth, low birthweight, and small for gestational age (SGA), when compared with fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology of this increased risk remains unclear; parental infertility, laboratory procedures (including embryo culture conditions and freezing-thawing processes), and endometrial preparation treatments might be involved. STUDY DESIGN, SIZE, DURATION: A multicentre epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national register of IVF from 2014 to 2018, including single deliveries resulting from fresh ET or FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres and included the vitrification media and devices, and the endometrial preparation protocols. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from 35 French ART centres, leading to the inclusion of a total of 72 789 fresh ET, 10 602 slow-freezing FET, and 39 062 vitrification FET. Main clinical outcomes were presented according to origin of the transferred embryos (fresh, slow frozen, or vitrified embryos) and endometrial preparations for FET (ovulatory or artificial cycles), comparing five different groups (fresh, slow freezing-ovulatory cycle, slow freezing-artificial cycle, vitrification-ovulatory cycle, and vitrification-artificial cycle). Foetal growth disorders were defined in live-born singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if <10th and ≥90th percentiles, respectively. Analyses were performed using linear mixed models with the ART centres as random effect. MAIN RESULTS AND THE ROLE OF CHANCE: Transfers led to, respectively, 19 006, 1798, and 9195 deliveries corresponding to delivery rates per transfer of 26.1%, 17.0%, and 23.5% after fresh ET, slow-freezing FET, and vitrification FET, respectively. FET cycles were performed in either ovulatory cycles (n = 21 704) or artificial cycles (n = 34 237), leading to 5910 and 10 322 pregnancies, respectively, and corresponding to pregnancy rates per transfer of 31.6% and 33.3%. A significantly higher rate of spontaneous miscarriage was observed in artificial cycles when compared with ovulatory cycles (33.3% versus 21.4%, P < 0.001, in slow freezing groups and 31.6% versus 21.8%, P < 0.001 in vitrification groups). Consequently, a lower delivery rate per transfer was observed in artificial cycles compared with ovulatory cycles both in slow freezing and vitrification groups (15.5% versus 18.9%, P < 0.001 and 22.8% versus 24.9%, P < 0.001, respectively). Among a total of 26 585 live-born singletons, 16 413 babies were born from fresh ET, 1644 from slow-freezing FET, and 8528 from vitrification FET. Birthweight was significantly higher in the FET groups than in the fresh ET group, with no difference between the two freezing techniques. Likewise, LGA rates were higher and SGA rates were lower in the FET groups compared with the fresh ET group whatever the method used for embryo freezing. In a multivariable analysis, the risk of LGA following FET was significantly increased in artificial compared with ovulatory cycles. In contrast, the risk of LGA was not associated with either the freezing procedure (vitrification versus slow freezing) or the embryo stage (cleaved embryo versus blastocyst) at freezing. Regarding the vitrification method, the risk of LGA was not associated with either the vitrification medium used or the embryo stage. LIMITATIONS, REASONS FOR CAUTION: No data were available on maternal context, such as parity, BMI, infertility cause, or maternal comorbidities, in the French national database. In particular, we cannot exclude that the increased risk of LGA observed following FET with artificial cycles may, at least partially, be associated with a confounding effect of some maternal factors. No information about embryo culture and incubation conditions was available. Most of the vitrification techniques were performed using the same device and with two main vitrification media, limiting the validity of a comparison of risk for LGA according to the device or vitrification media used. WIDER IMPLICATIONS OF THE FINDINGS: Our results seem reassuring, since no potential foetal growth disorders following embryo vitrification in comparison with slow freezing were observed. Even if other factors are involved, the endometrial preparation treatment seems to have the greatest impact on LGA risk following FET. FET during ovulatory cycles could minimize the risk for foetal growth disorders. STUDY FUNDING/COMPETING INTEREST(S): This work has received funding from the French Biomedicine Agency (Grant number: 19AMP002). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Infertilidade , Nascimento Prematuro , Gravidez , Masculino , Feminino , Recém-Nascido , Humanos , Peso ao Nascer , Congelamento , Estudos Retrospectivos , Criopreservação/métodos , Idade Gestacional , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Taxa de Gravidez , Infertilidade/etiologia , Transtornos do Crescimento/etiologiaRESUMO
BACKGROUND: The present study aimed to explore the maternal and perinatal risks in cases of monozygotic twins (MZT) following frozen-thawed embryo transfer (FET). METHODS: All twin births that were conceived following FET from 2007 to 2021 at Shanghai Ninth People's Hospital in Shanghai, China were retrospectively reviewed. The exposure variable was twin type (monozygotic and dizygotic). The primary outcome was the incidence of neonatal death while secondary outcomes included hypertensive disorders of pregnancy, gestational diabetes, intrahepatic cholestasis of pregnancy, placenta previa, placental abruption, preterm premature rupture of the membranes, Cesarean delivery, gestational age, birth weight, weight discordance, stillbirth, birth defects, pneumonia, respiratory distress syndrome, necrotizing enterocolitis, and neonatal jaundice. Analysis of the outcomes was performed using logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The causal mediation analysis was conducted. A doubly robust estimation model was used to validate the results. Kaplan-Meier method was used to calculate survival probability. The sensitivity analysis was performed with a propensity score-based patient-matching model. RESULTS: Of 6101 dizygotic twin (DZT) and 164 MZT births conceived by FET, MZT showed an increased risk of neonatal death based on the multivariate logistic regression models (partially adjusted OR: 4.19; 95% CI, 1.23-10.8; fully adjusted OR: 4.95; 95% CI, 1.41-13.2). Similar results were obtained with the doubly robust estimation. Comparing MZT with DZT, the neonatal survival probability was lower for MZT (P < 0.05). The results were robust in the sensitivity analysis. Females with MZT pregnancies exhibited an elevated risk of preterm premature rupture of the membranes (adjusted OR: 2.42; 95% CI, 1.54-3.70). MZT were also associated with higher odds of preterm birth (prior to 37 weeks) (adjusted OR: 2.31; 95% CI, 1.48-3.67), low birth weight (adjusted OR: 1.92; 95% CI, 1.27-2.93), and small for gestational age (adjusted OR: 2.18; 95% CI, 1.21-3.69) in the fully adjusted analyses. The effect of MZT on neonatal death was partially mediated by preterm birth and low birth weight (P < 0.05). CONCLUSIONS: This study indicates that MZT conceived by FET are related to an increased risk of neonatal death, emphasizing a potential need for comprehensive antenatal surveillance in these at-risk pregnancies.
Assuntos
Ruptura Prematura de Membranas Fetais , Gêmeos Monozigóticos , Feminino , Humanos , Recém-Nascido , Gravidez , China , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Morte Perinatal , Placenta , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate whether laser-mediated assisted hatching (AH) performed on vitrified/warmed blastocysts before embryo transfer can improve live birth rate. DESIGN: The "pArtiaL zonA pelluciDa removal by assisteD hatchINg of blastocysts (ALADDIN)" is a 2-center comparative study with a parallel randomized controlled design. SETTING: University hospital. PATIENTS: Participants were recruited between September 2018 and November 2021. They were aged 18-39 years, underwent nondonor in vitro fertilization cycles, and were scheduled for elective single embryo transfer with vitrified/warmed blastocysts. Those with uterine abnormalities, body mass index of >35 kg/m2, severe male factor infertility, or performing preimplantation genetic testing were excluded. INTERVENTION: Assisted hatching was performed using a 1,480 nm diode laser, removing approximately one-third of the zona pellucida with continuous 0.2 ms pulses applied from the 1-5 o'clock positions. MAIN OUTCOME MEASURES: The primary outcome was the live birth rate. Secondary end points included clinical pregnancy, miscarriage, multiple pregnancies, preterm births, obstetric and neonatal complications, and congenital anomalies. RESULTS: Overall, 698 participants met the inclusion criteria and were randomized: 352 patients were assigned to the AH arm and 346 to the control arm. Of the participants, 105 (29.8%) and 101 (29.2%), respectively, achieved a live birth after treatment. The relative risk of live birth in patients with vitrified/warmed blastocysts treated with AH was 1.02 (95% confidence interval, 0.86-1.19). Exploratory subgroup analyses for women's age, recruiting centers, indications for in vitro fertilization, method of insemination, blastocyst quality, and days of blastocyst development failed to highlight any clinical situation that could benefit from AH in thawed blastocysts. CONCLUSION: In patients undergoing frozen embryo transfer with vitrified/warmed blastocysts, laser AH does not improve the live birth rate. Further studies are required to rule out milder but potentially interesting benefits in specific subgroups of patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03623659.
Assuntos
Blastocisto , Nascido Vivo , Taxa de Gravidez , Vitrificação , Humanos , Feminino , Adulto , Gravidez , Criopreservação/métodos , Zona Pelúcida , Adulto Jovem , Fertilização in vitro/métodos , Infertilidade/terapia , Infertilidade/fisiopatologia , Infertilidade/diagnóstico , Adolescente , Transferência Embrionária/métodos , Transferência Embrionária/efeitos adversos , Resultado do Tratamento , Técnicas de Cultura Embrionária , Transferência de Embrião Único/métodos , Transferência de Embrião Único/efeitos adversos , Lasers , MasculinoRESUMO
OBJECTIVE: To examine the relationship between the day of embryo cryopreservation and large for gestational age (LGA) infants in women undergoing frozen embryo transfers (FETs) after cryopreservation on days 2-7 after fertilization and to compare the risk of the day of embryo cryopreservation to other possible risk factors of LGA after FET cycles. DESIGN: Retrospective cohort study. SETTING: Society of Assisted Reproduction Clinical Outcomes Reporting System. PATIENTS: Women undergoing FET cycles. INTERVENTION: Day of cryopreservation. MAIN OUTCOME MEASURE: Singleton LGA infant. RESULTS: A total of 33,030 (18.2%) FET cycles in the study group (n = 181,592) resulted in LGA infants during the study period of 2014-2019. There was an increase in LGA risk when cryopreservation was performed from day 2 (13.7%) to days 3-7 (14.4%, 15.0%, 18.2%, 18.5%, and 18.9%). In the log-binomial model, the risk increased compared with days 2-3 combined when cryopreservation was performed on days 5-7 (adjusted relative risk [aRR] 1.32, 95% confidence interval [CI] 1.22-1.44 for day 5, aRR 1.34, 95% CI 1.23-1.46 for day 6, and aRR 1.42, 95% CI 1.25-1.61 for day 7). Other factors most associated with LGA risk in the log-binomial model were preterm parity of >3 compared with 0 (aRR 1.82, 95% CI 1.24-2.69) and body mass index (BMI) of >35 kg/m2 compared with normal weight (aRR 1.94, 95% CI 1.88-2.01). Increasing gravity, parity, BMI, number of oocytes, and embryo grade were also associated with LGA in this model. Asian, Black, Hispanic, and combined Hawaiian and Pacific Islander were protective factors in the model compared with White patients. Low BMI (<18.5 kg/m2) was also considered a protective factor in the model compared with normal BMI. CONCLUSION: Duration of embryo culture was associated with an increased risk of LGA in this study cohort when controlling for known confounders such as maternal BMI and parity. This study sheds new light on the possible link between FET and LGA infants.
Assuntos
Criopreservação , Técnicas de Cultura Embrionária , Transferência Embrionária , Humanos , Feminino , Transferência Embrionária/métodos , Transferência Embrionária/estatística & dados numéricos , Transferência Embrionária/efeitos adversos , Estudos Retrospectivos , Gravidez , Adulto , Fatores de Tempo , Fatores de Risco , Recém-Nascido , Idade Gestacional , Macrossomia Fetal/epidemiologia , Peso ao Nascer , Fertilização in vitro/efeitos adversos , Medição de Risco , Infertilidade/terapia , Infertilidade/fisiopatologia , Infertilidade/diagnósticoRESUMO
OBJECTIVE: To study the impact of unhealthy air quality from the 2020 Oregon wildfires on outcomes for patients undergoing in vitro fertilization (IVF) treatment. DESIGN: A retrospective cohort study. SETTING: A university-based fertility clinic. PATIENTS: Subjects were undergoing IVF treatment from the 6 weeks preceding the wildfires through a 10-day exposure period. Cohorts were classified on the basis of whether subjects experienced patient and/or laboratory exposure to unhealthy air quality. Patient exposure was defined as at least 4 days of ovarian stimulation overlapping with the exposure, and laboratory exposure was defined as at least 2 days of IVF treatment and embryogenesis overlapping with the exposure. The unexposed cohort consisted of remaining subjects without defined exposure, with cycles in the 6 weeks preceding the wildfires. As some subjects had dual exposure and appeared in both patient and laboratory exposure cohorts, each cohort was separately compared with the unexposed control cohort. INTERVENTION: A 10-day period of unhealthy air quality caused by smoke plumes from a wildfire event. MAIN OUTCOME MEASURES: The primary outcome was the blastulation rate. Secondary outcomes included fertilization rate, number of blastocysts obtained, and cycles with no blastocysts frozen or transferred. RESULTS: Sixty-nine subjects underwent ovarian stimulation and IVF treatment during the 6 weeks preceding the wildfires through the 10-day period of unhealthy air quality. Of these, 15 patients were in the laboratory exposure cohort, 16 were in the patient exposure cohort, and 44 were unexposed. Six subjects appeared in both laboratory and patient exposure cohorts. Although neither exposure cohort had significantly decreased blastulation rate compared with the unexposed, the median number of blastocysts obtained was significantly lower in the laboratory exposure cohort than the unexposed group (2 [range 0-14] vs. 4.5 [range 0-21], respectively). The laboratory exposure cohort had significantly more cycles with no blastocysts obtained (3/15 [20%] vs. 1/44 [2%]). There were no significant differences in IVF treatment outcomes between patient exposure and unexposed cohorts. These findings persisted after controlling for age. There were no significant differences in pregnancy outcomes observed after embryo transfer between the exposure group and the unexposed group. CONCLUSION: For a cohort of patients undergoing IVF treatment, an acute episode of outside wildfire smoke exposure during fertilization and embryogenesis was associated with decreased blastocyst yield.
Assuntos
Blastocisto , Fertilização in vitro , Fumaça , Incêndios Florestais , Humanos , Feminino , Estudos Retrospectivos , Fertilização in vitro/efeitos adversos , Adulto , Gravidez , Fumaça/efeitos adversos , Indução da Ovulação/efeitos adversos , Taxa de Gravidez , Transferência Embrionária/efeitos adversos , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Resultado do Tratamento , Oregon/epidemiologia , Fatores de Risco , Fatores de Tempo , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , FertilidadeRESUMO
BACKGROUND: The prevalence of ectopic pregnancy after assisted reproduction is notably high, posing a significant threat to the life safety of pregnant women. Discrepancies in published results and the lack of a comprehensive description of all risk factors have led to ongoing uncertainties concerning ectopic pregnancy after assisted reproduction. OBJECTIVE: This study aimed to understand the risk factors for ectopic pregnancy after in vitro fertilization-embryo transfer in the Chinese population and provide a reference for targeted prevention and treatment. METHODS: A comprehensive search of the China National Knowledge Infrastructure, Wang fang Database, China Science Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Web of Science, and Embase was conducted to identify relevant literature on the risk factors for ectopic pregnancy in Chinese women after assisted reproductive technology in Chinese women. A meta-analysis of the included studies was performed using Stata17. RESULTS: Overall, 34 articles were included in the analysis. The risk factors for ectopic pregnancy after in vitro fertilization-embryo transfer in the Chinese population included a thin endometrium on the day of HCG administration and embryo transplantation, a history of ectopic pregnancy, secondary infertility, a history of induced abortion, polycystic ovary syndrome, decreased ovarian reserve, tubal factor infertility, cleavage stage embryo transfer, fresh embryo transfer, artificial cycle protocols, elevated estradiol levels on the day of human chorionic gonadotropin administration, a history of tubal surgery, two or more number of embryo transfers, previous pregnancy history, and a history of pelvic surgery. CONCLUSION: This study clarified the factors influencing ectopic pregnancy after in vitro fertilization and embryo transfer in the Chinese population, focusing on high-risk groups. Targeted and personalized intervention measures should be adopted to prevent and detect the disease early to reduce its incidence and harm. TRIAL REGISTRATION: The protocol for this view was registered in PROSPERO (CRD42023414710).
Assuntos
Infertilidade Feminina , Gravidez Ectópica , Gravidez , Feminino , Humanos , Gravidez Ectópica/epidemiologia , Gravidez Ectópica/etiologia , Transferência Embrionária/efeitos adversos , Fertilização in vitro/efeitos adversos , Fatores de Risco , Taxa de Gravidez , Infertilidade Feminina/etiologia , Estudos RetrospectivosRESUMO
RESEARCH QUESTION: Is there an association between intrauterine haematoma (IUH) and pregnancy outcomes in patients who undergo fetal reduction after double embryo transfer (DET), and if so, what is the relationship between IUH-related characteristics and pregnancy outcomes? DESIGN: Clinical information and pregnancy outcomes of women who underwent fetal reduction after DET were analysed. Patients with other systematic diseases, ectopic pregnancy or heterotopic pregnancy, monochorionic twin pregnancies and incomplete data were excluded. Stratification of IUH pregnancies was undertaken based on IUH-related characteristics. The main outcome was incidence of fetal demise (<24 weeks), with other adverse pregnancy outcomes considered as secondary outcomes. RESULTS: Thirty-four IUH patients and 136 non-IUH patients who underwent fetal reduction after DET were included based on a 1:4 match for age, cycle type and fertilization method. IUH patients had a higher incidence of early fetal demise (20.6% versus 7.4%, Pâ¯=â¯0.048), threatened abortion (48.1% versus 10.3%, P<0.001) and postpartum haemorrhage (PPH; 14.8% versus 4.0%, Pâ¯=â¯0.043) compared with non-IUH patients. IUH was an independent risk factor for early fetal demise [adjusted OR (aOR) 3.34, 95% CI 1.14-9.77] and threatened abortion (aOR 8.61, 95% CI 3.28-22.61) after adjusting for potential confounders. IUH pregnancies undergoing fetal reduction that resulted in miscarriage had larger IUH volumes and earlier diagnosis (both P < 0.03). However, IUH characteristics (i.e. volume, changing pattern, presence or absence of cardiac activity) were not associated with threatened abortion or PPH. CONCLUSIONS: Fetal reduction should be performed with caution in IUH pregnancies after DET as the risk of fetal demise is relatively high. Particular attention should be given to IUH patients with early signs of threatened abortion and inevitable fetal demise.
Assuntos
Aborto Espontâneo , Ameaça de Aborto , Gravidez , Humanos , Feminino , Resultado da Gravidez , Redução de Gravidez Multifetal , Gravidez de Gêmeos , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Natimorto , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Hematoma/epidemiologia , Hematoma/etiologia , Estudos RetrospectivosRESUMO
Hydatidiform mole and coexisting fetus is a very rare condition of which etiology is still inconclusive. It may occur after assisted reproduction, often leading to the death of normal embryos and other serious complications. We report a case of partial hydatidiform mole and coexisting fetus after frozen embryo transplantation. More than two months after the patient underwent transplantation with two blastocysts (scored 4AB and 4BC), B-ultrasound showed a single live fetus with a large dense dotted strong echo area. The patient was treated with chemotherapy after the termination of pregnancy due to persistently increased human chorionic gonadotropin levels. Many studies have described trophoblast quality as a strong predictor of pregnancy. In the case in question, in addition to partial hydatidiform mole caused by multiple sperm entering the egg, we also speculate that the condition may be related to the poor quality of the trophoblastic ectoderm of the transferred embryo. In the process of assisted reproduction, the transfer of embryos with poor trophoblastic ectoderm in multiple embryo transfers may adversely affect pregnancy outcomes.
Assuntos
Mola Hidatiforme , Neoplasias Uterinas , Gravidez , Feminino , Masculino , Humanos , Sêmen , Mola Hidatiforme/terapia , Feto , Transferência Embrionária/efeitos adversosRESUMO
The objective was to analyze the effect of paternal body mass index (BMI) on maternal and child-health outcomes of singletons after frozen-thawed embryo transfer (FET) cycles. A retrospective cohort study was conducted between January 2019 and December 2021. Pregnancy, perinatal complications and neonatal outcomes were compared among different paternal BMI. Multivariate logistic regression was performed to evaluate the relationship between different paternal BMI and pregnancy, obstetric and neonatal outcomes. The paternal normal group was more likely to suffer from gestational hypertension than the paternal obesity group (3.59% vs. 2.42%), and paternal underweight group was more likely to suffer from preeclampsia than the other three groups (11.63% vs. 4.43%, 7.57%, 4.03%). Birthweight among infants in the paternal overweight categories was significantly higher than infants in the paternal normal weight categories. The rate of foetal macrosomia was higher among infants in the paternal overweight (12.36%) category, while lower among infants in the paternal underweight categories (2.33%). The incidence of macrosomia in the paternal overweight categories (aOR 1.527, 95% CI 1.078-2.163) was significantly higher than those normal controls after adjustment for known confounding factors. The rates of LGA babies were higher in the paternal overweight category (aOR 1.260, 95% CI 1.001-1.587) compared with those in the paternal normal weight category, before and after adjustment. The results suggest that parental pre-pregnancy overweight or obesity has an adverse effect on the perinatal complications and neonatal outcomes.
Assuntos
Sobrepeso , Magreza , Lactente , Recém-Nascido , Feminino , Gravidez , Humanos , Índice de Massa Corporal , Estudos Retrospectivos , Sobrepeso/epidemiologia , Obesidade , Transferência Embrionária/efeitos adversos , Avaliação de Resultados em Cuidados de SaúdeRESUMO
STUDY QUESTION: Are there growth differences between singleton children born after frozen embryo transfer (FET), fresh embryo transfer (ET), and natural conception (NC)? SUMMARY ANSWER: Adolescent boys born after FET have a higher mean proportion and increased odds of overweight compared to those born after fresh ET. WHAT IS KNOWN ALREADY: Children born after FET have higher mean birthweights and an increased risk of large-for-gestational-age compared to those born after fresh ET and even NC. This raises questions about possible growth differences later in childhood. Previous studies on child growth after FET report partly conflicting results and lack long-term data until adolescence. STUDY DESIGN, SIZE, DURATION: This was a cohort study based on national population-based registers, the Finnish Medical Birth Register and the Register of Primary Health Care visits, including singletons born after FET (n = 1825), fresh ET (n = 2933), and NC (n = 31â136) in Finland between the years 1995 and 2006. PARTICIPANTS/MATERIALS, SETTING, METHODS: The proportions of overweight (i.e. age- and sex-adjusted ISO-BMI for children ≥ 25) were compared between the groups. Odds ratios (ORs) and adjusted odds ratios (aORs) of overweight were calculated. Adjustments were made for birth year, preterm birth, maternal age, parity, and socioeconomic status. Mean heights, weights, and BMIs were compared between the groups each year between the ages of 7 and 18. MAIN RESULTS AND THE ROLE OF CHANCE: FET boys had a higher mean proportion of overweight (28%) compared to fresh ET (22%, P < 0.001) and NC (26%, P = 0.014) boys. For all ages combined, the aOR of overweight was increased (1.14, 95% CI 1.02-1.27) for FET boys compared to fresh ET boys. For girls, the mean proportions of overweight were 18%, 19%, and 22% for those born after FET, fresh ET, and NC, respectively (P = 0.169 for FET vs fresh ET, P < 0.001 for FET vs NC). For all ages combined, FET girls had a decreased aOR of overweight (0.89, 95% CI 0.80-0.99) compared to NC girls. Growth measurements were available for 6.9% to 30.6% of FET boys and for 4.7% to 29.4% of FET girls at different ages. LIMITATIONS, REASONS FOR CAUTION: Unfortunately, we were not able to adjust for parental anthropometric characteristics. The growth data were not available for the whole cohort, and the proportion of children with available measurements was limited at the start and end of the follow-up. During the study period, mainly cleavage stage embryos were transferred, and slow freezing was used for ART. WIDER IMPLICATIONS OF THE FINDINGS: The risk of overweight among FET boys warrants further research. Future studies should aim to investigate the mechanisms that explain this sex-specific finding and combine growth data with long-term health data to explore the possible risks of overweight and cardiometabolic disease in adulthood. STUDY FUNDING/COMPETING INTEREST(S): Funding was obtained from the Päivikki and Sakari Sohlberg Foundation, the Alma and K.A. Snellman Foundation (personal grants to A.M.T.), and the Finnish Government Research Funding. The funding sources were not involved in the planning or execution of the study. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Sobrepeso , Nascimento Prematuro , Recém-Nascido , Adolescente , Masculino , Criança , Feminino , Gravidez , Humanos , Finlândia/epidemiologia , Estudos de Coortes , Sobrepeso/epidemiologia , Transferência Embrionária/efeitos adversosRESUMO
OBJECTIVE: To investigate whether endometrial thickness (EMT) acts as a contributing factor to adverse perinatal outcomes in programmed frozen-thawed embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SETTING: University-based reproductive medical center. SUBJECT: The study included singleton live births resulting from programmed FET cycles that took place between January 2017 and April 2022 (N = 2,275 cycles). EXPOSURE: The EMT measurement conducted on the day of progesterone initiation was utilized. Programmed FET cycles with EMT <7 mm were excluded from consideration. All included subjects were divided into 4 groups on the basis of the 10th, 50th, and 90th percentiles of EMT: group â (EMT ≤8 mm, n = 193), group â ¡ (EMT = 8.1-10 mm, n = 1,261), group â ¢ (EMT = 10.1-12 mm, n = 615), and group â £ (EMT >12 mm, n = 206). After adjusting for patient demographics and FET parameters, logistic regression analysis and restricted cubic spline were used to investigate the relationship between EMT and perinatal outcomes. The group â ¡ (EMT = 8.1-10 mm) served as a reference. MAIN OUTCOME MEASURE(S): The primary outcome measure was the hypertensive disorders of pregnancy (HDP). Secondary outcomes included gestational diabetes mellitus, cesarean delivery, placenta previa, premature rupture of membrane, birthweight, preterm birth, low birthweight, macrosomia, small for gestational age, large for gestational age and neonatal morbidity. RESULTS(S): The incidence of HDP was substantially elevated in group â £ when compared with the other groups (5.7% vs. 4.1% vs. 5.7% vs. 9.7% for groups â -â £, respectively). In addition, group I displayed a higher incidence of cesarean deliveries, whereas both group I and group IV exhibited an elevated prevalence of placenta previa. After adjusting for confounding factors, patients in group IV exhibited a significantly increased risk of HDP (adjusted odds ratio [OR] = 2.03, 95% confidence interval [CI] 1.13-3.67) as compared with patients in the reference group. The restricted cubic spline model revealed a nonlinear association between EMT and the odds of HDP on continuous scales. In comparison to women with an EMT of 9.5 mm, there was no significant change in the risk of HDP in women with EMT between 7 and 11 mm, as indicated by adjusted ORs of 1.37 (95% CI 0.41-4.52), 1.34 (95% CI 0.73-2.47), 1.13 (95% CI 0.79-1.62), 1.04 (95% CI 0.87-1.25), and 1.46 (95% CI 0.81-2.65), respectively. However, the risk of HDP was significantly higher in women with EMT ranging from 12 to 15 mm, with adjusted ORs of 1.86 (95% CI 1.03-3.35), 2.33 (95% CI 1.32-4.12), 2.92 (95% CI 1.52-5.60), and 3.62 (95% CI 1.63-8.04), respectively. CONCLUSION(S): This study demonstrated a noteworthy association between EMT and adverse perinatal outcomes during the programmed FET cycles. Specifically, a thick endometrium (EMT >12 mm) was independently associated with an increased risk of developing HDP, whereas the optimal EMT for reducing the risk of HDP was at around 9-10 mm.
Assuntos
Hipertensão Induzida pela Gravidez , Placenta Prévia , Nascimento Prematuro , Gravidez , Recém-Nascido , Humanos , Feminino , Estudos Retrospectivos , Peso ao Nascer , Hipertensão Induzida pela Gravidez/epidemiologia , Placenta Prévia/etiologia , Nascimento Prematuro/etiologia , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , EndométrioRESUMO
The aim of this study was to investigate if variation in endometrial thickness affects clinical pregnancy and live birth rates among patients undergoing single euploid embryo transfer (SET). A retrospective review of IVF cycles performed at a single private fertility institution between 2015 and 2020 was performed. Patients with normal uterine anatomy undergoing their first SET of a euploid embryo undergoing their first cycle at the center were included, for a total of 796 cycles. Endometrial thickness was measured by transvaginal ultrasound following 10-14 days of estradiol exposure. Specific infertility diagnoses did not significantly impact endometrial lining thickness with means across diagnoses ranging from 9.3 to 11.0 mm. Endometrial thickness was grouped into five categories: < 8 mm, 8-10 mm, 10-13 mm, 13-15 mm, and ≥ 15 mm. Using 8-10 mm as the reference group, the odds ratio of live birth was 0.5, 1.22, 1.05, and 1.05 for < 8 mm, 10-13 mm, 13-15 mm, and ≥ 15 mm groups, respectively. Risk of first trimester miscarriage was equivalent across groups. There was a trend toward an increased rate of biochemical pregnancies in patients with a < 8 mm and ≥ 15 mm endometrium; however, this was not statistically significant. The clinical pregnancy and live birth rate were lowest in patients with < 8-mm endometrial thickness. For single euploid embryo transfers, an endometrial lining greater than or equal to 8 mm confers optimal live birth rates following a medicated FET cycle. These data confirm the findings of prior studies in fresh embryo transfers without the confounders of supraphysiologic ovarian hormone concentrations and genetically untested embryos.
Assuntos
Aborto Espontâneo , Transferência de Embrião Único , Gravidez , Feminino , Humanos , Taxa de Gravidez , Transferência Embrionária/efeitos adversos , Coeficiente de Natalidade , Nascido Vivo , Estudos Retrospectivos , Fertilização in vitro/efeitos adversosRESUMO
Assisted reproduction is a risk factor for adnexal torsion due to ovarian hyperstimulation and increased incidence of twin pregnancy. Both risk factors can be eliminated in frozen embryo transfers, but in our case ovarian torsion occurred after the use of an aromatase inhibitor (Femara) in endometrium preparation due to the presence of corpus luteum. Case presentation: G2P1+0 presented at 7 weeks gestation after vitrified-warmed embryo transfer with right loin pain and mild right iliac pain and tenderness. Ultrasound examination revealed transient or incomplete ovarian torsion. The presentation of the case was somewhat misleading and the transient nature of the torsion provided an opportunity for the conservative management of the case. In conclusion, ovarian torsion is still an undesired event, even after single embryo transfers and in vitrified-warmed cycles. Clinical and ultrasound follow-up precluded the need for surgery in our case.
Assuntos
Torção Ovariana , Gestantes , Gravidez , Feminino , Humanos , Criopreservação , Estudos Retrospectivos , Transferência Embrionária/efeitos adversos , DorRESUMO
As a result of epigenetic changes, children conceived by assisted reproduction may be at risk of premature cardiovascular aging with notably increased blood pressures. Their cardiovascular autonomic nervous function is unknown. Therefore, this study investigated the cardiovascular autonomic nervous function in 8-12-yr-old children (51% girls) conceived naturally (n = 33) or by assisted reproduction with frozen (n = 34) or fresh (n = 38) embryo transfer by evaluating heart rate variability, during rest; from provocation maneuvers; and from baroreflex function. Heart rate and blood pressure response to provocation maneuvers and baroreflex function were comparable between children conceived naturally or by assisted reproduction. The mean RR-interval and high-frequency component of heart rate variability were lower in children conceived by assisted reproduction than in children conceived naturally. Children conceived by fresh embryo transfer had â¼17% lower heart rate-corrected standard deviation of normal-to-normal R-R intervals; â¼22% lower heart rate-corrected square root of the mean of the squared difference between successive R-R intervals; and â¼37% higher low-frequency/high-frequency ratio than naturally conceived children. Children conceived by assisted reproduction still had lower heart rate variability and vagal modulation than naturally conceived children after adjustment for confounders. Thus, these results raise the possibility of sympathetic predominance in children conceived by assisted reproduction. Therefore, it is important to reproduce these results in larger and older cohorts as sympathetic predominance relates with cardiovascular and metabolic diseases.NEW & NOTEWORTHY We observed that children conceived by assisted reproductive technology (both frozen and fresh embryo transfer) had lowered heart rate variability during rest as compared with children conceived naturally. During physiological stress maneuvers, however, the cardiovascular autonomic nervous regulation was comparable between children conceived by assisted reproductive technologies and naturally. Our findings highlight the potential that lowered heart rate variability during rest in children conceived by assisted reproductive technologies may precede premature hypertension.
Assuntos
Hipertensão , Nascimento Prematuro , Criança , Feminino , Humanos , Masculino , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Técnicas de Reprodução Assistida/efeitos adversos , BarorreflexoRESUMO
The number of frozen embryo transfer (FET) cycles is increasing rapidly worldwide. Different endometrial preparations for FET result in comparable live birth rates. However, several recent publications have reported higher maternal risks for hypertensive disorders of pregnancy (HDP), pre-eclampsia and postpartum haemorrhage (PPH) in programmed cycles (PC-FET) compared with natural cycles and modified natural cycles with an intact corpus luteum. Nevertheless, PC-FET is frequently used in ovulatory women despite the increased risks for HDP, pre-eclampsia and PPH. Although randomized controlled studies have been suggested, PC-FET raises several methodological problems. Large study populations would be required to investigate the outcomes in question, and the inclusion of ovulatory women, where the intervention may increase the risk of a negative outcome, is ethically troublesome. In the authors' opinion, the existing evidence from large observational studies and systematic reviews is sufficiently strong to recommend an endometrial preparation strategy that aims to maintain or stimulate the corpus luteum to minimize the risk of HDP and pre-eclampsia after FET cycles.
Assuntos
Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Criopreservação/métodos , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Coeficiente de Natalidade , Corpo Lúteo , Estudos Retrospectivos , Taxa de GravidezRESUMO
IMPORTANCE: Previous reviews have shown that a history of cesarean section (CS) is associated with a worse in vitro fertilization (IVF) prognosis. To date, whether the decline in the IVF chances of success should be attributed to the CS procedure itself or to the presence of isthmocele remains to be clarified. OBJECTIVE: To summarize the available evidence regarding the impact of isthmocele on IVF outcomes. DATA SOURCES: Electronic databases and clinical registers were searched until May 30, 2023. STUDY SELECTION AND SYNTHESIS: Observational studies were included if they assessed the effect of isthmocele on IVF outcomes. Comparators were women with isthmocele and women without isthmocele with a previous CS or vaginal delivery. Study quality was assessed using the modified Newcastle-Ottawa Scale. MAIN OUTCOMES: The primary outcome was the live birth rate (LBR). The effect measures were expressed as adjusted odds ratios (aORs) and unadjusted odds ratios (uORs) with 95% confidence intervals (95% CIs). The body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation working group methodology. RESULTS: Eight studies (n = 10,873 patients) were included in the analysis. Women with isthmocele showed a lower LBR than both women with a previous CS without isthmocele (aOR, 0.62; 95% CI, 0.53-0.72) and those with a history of vaginal delivery (aOR, 0.55; 95% CI, 0.42-0.71). The LBRs in women with a previous CS without isthmocele and those with a history of vaginal delivery were similar (aOR, 0.74; 95% CI, 0.47-1.15). Subgroup analysis suggested a negative effect of the intracavitary fluid (ICF) in women with isthmocele on the LBR (uOR, 0.36; 95% CI, 0.18-0.75), whereas the LBRs in women without ICF and those without isthmocele were similar (uOR, 0.94; 95% CI, 0.61-1.45). CONCLUSION AND RELEVANCE: We found moderate quality of evidence (Grading of Recommendations Assessment, Development and Evaluation grade 3/4) supporting a negative impact of isthmocele, but not of CS per se, on the LBR in women undergoing IVF. The adverse effect of isthmocele on IVF outcomes appears to be worsened by ICF accumulation before embryo transfer. CLINICAL TRIAL REGISTRATION NUMBER: CRD42023418266.