Study on the optimal time limit of frozen embryo transfer and the effect of a long-term frozen embryo on pregnancy outcome.

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), and ≥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 (OR < 1, aOR < 1, P < .05). Furthermore, an elevated incidence of ectopic pregnancy was observed (OR > 1, aOR > 1), notably significant after 6 years of freezing time [aOR = 4.141, 95% confidence intervals (1.013-16.921), P = .05]. Cryopreservation exceeding 1 year was associated with an increased risk of early miscarriage and preterm birth (OR > 1, aOR > 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.

Is large for gestational age in singletons born after frozen embryo transfer associated with freezing technique or endometrial preparation protocol? A longitudinal national French study.

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.

Maternal and perinatal risks for monozygotic twins conceived following frozen-thawed embryo transfer: a retrospective cohort study.

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.

Partial hydatidiform mole and coexisting fetus after frozen embryo transplantation: a case report.

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.

Growth of singletons born after frozen embryo transfer until early adulthood: a Finnish register study.

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 = 31 136) 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.

Pregnancy outcomes of fetal reduction in patients with intrauterine haematoma following double embryo transfer.

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%, P = 0.048), threatened abortion (48.1% versus 10.3%, P<0.001) and postpartum haemorrhage (PPH; 14.8% versus 4.0%, P = 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.

Effect of paternal body mass index on maternal and child-health outcomes of singletons after frozen-thawed embryo transfer cycles: a retrospective study.

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.

Risk factors of ectopic pregnancy after in vitro fertilization-embryo transfer in Chinese population: A meta-analysis.

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).

Thick endometrium is associated with hypertensive disorders of pregnancy in programmed frozen-thawed embryo transfers: a retrospective analysis of 2,275 singleton deliveries.

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 Ⅰ (EMT ≤8 mm, n = 193), group Ⅱ (EMT = 8.1-10 mm, n = 1,261), group Ⅲ (EMT = 10.1-12 mm, n = 615), and group Ⅳ (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 Ⅱ (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 Ⅳ when compared with the other groups (5.7% vs. 4.1% vs. 5.7% vs. 9.7% for groups Ⅰ-Ⅳ, 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.

Isthmocele, not cesarean section per se, reduces in vitro fertilization success: a systematic review and meta-analysis of over 10,000 embryo transfer cycles.

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.

Higher live birth rates are associated with a normal body mass index in preimplantation genetic testing for aneuploidy frozen embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System study.

OBJECTIVE: To determine whether body mass index (BMI) was associated with live birth in patients undergoing transfer of frozen-thawed preimplantation genetic testing for aneuploidy (PGT-A) embryos. DESIGN: Retrospective cohort study of cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. SUBJECTS: All autologous and donor recipient PGT-A-tested cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System from 2014 to 2017. INTERVENTION(S): Body mass index. MAIN OUTCOME MEASURE(S): The primary outcome measure was the live birth rate, and the secondary outcome measures were the clinical pregnancy and biochemical pregnancy rates. Multivariable generalized additive mixed models and log-binomial models were used to model the relationship between BMI and outcome measures. RESULT(S): A total of 77,018 PGT-A cycles from 55,888 patients were analyzed. Of these cycles, 70,752 were autologous, and 6,266 were donor recipient. In autologous cycles, a statistically significant and clear nonlinear relationship was observed between the BMI and live birth rates, with the highest birth rates observed for the BMI range of 23-24.99 kg/m2. When using 23-24.99 kg/m2 as the referent, other BMI ranges demonstrated a lower probability of live birth and clinical pregnancy that continued to decrease as the BMI moved further from the reference value. Patients with a BMI of <18.5 kg/m2 had a 11% lower probability of live birth, whereas those with a BMI of ≥40 kg/m2 had a 27% lower probability than the referent. CONCLUSION(S): A normal-weight BMI range of 23-24.99 kg/m2 was associated with the highest probability of clinical pregnancy and live birth after a frozen-thawed PGT-A-tested blastocyst transfer in both autologous and donor recipient cycles. A BMI outside the range of 23-24.99 kg/m2 is likely associated with a malfunction in the implantation process, which is presumed to be related to a uterine factor and not an oocyte factor, as both autologous and donor recipient cycle outcomes were associated similarly with the BMI of the intended parent.

Endometrial preparation protocols prior to frozen embryo transfer - convenience or safety?

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.

Association between oocyte donors' or recipients' body mass index and clinical outcomes after first single blastocyst transfers-the uterus is the most affected.

OBJECTIVE: To assess whether high body mass index (BMI) in either oocyte donors or recipients is associated with poorer outcomes after the first single blastocyst transfer. DESIGN: Retrospective study including 1,394 first blastocyst single embryo transfers (SETs) conducted by 1,394 recipients during oocyte donation cycles with the gametes retrieved from 1,394 women (January 2019-July 2021). Four BMI clusters were defined for both donors and recipients (underweight: <18.5 kg; normal weight: 18.5-24.9 kg; overweight: 25-29.9 kg; and obese: ≥30 kg). SETTING: Network of private IVF centers. PATIENTS: A total of 1,394 recipients aged 42.4 ± 4.0 and with a BMI of 23.2 ± 3.8 kg/m2, and 1,394 donors aged 26.1 ± 4.2 and with a BMI of 21.9 ± 2.5 kg/m2. INTERVENTION: All oocytes were vitrified at 2 egg banks and warmed at 8 in vitro fertilization clinics that were part of the same network. Intracytoplasmic sperm injection, blastocyst culture, and either fresh or vitrified-warmed SETs were conducted. Putative confounders were investigated, and the data were adjusted through regression analyses. MAIN OUTCOME MEASURES: The primary outcome was the live birth rate (LBR) per SET according to donors' and/or recipients' BMI. The main secondary outcome was the miscarriage rate (<22 gestational weeks) per clinical pregnancy. RESULTS: The LBR per blastocyst SET showed no significant association with donors' BMI. Regarding recipients' BMI, instead, the multivariate odds ratio was significant in obese vs. normal-weight recipients (0.58, 95% confidence interval, 0.37-0.91). The miscarriage rate per clinical pregnancy was also significantly associated with recipients' obesity, with a multivariate odds ratio of 2.31 (95% confidence interval, 1.18-4.51) vs. normal-weight patients. A generalized additive model method was used to represent the relationship between predicted LBR or miscarriage rates and donors' or recipients' BMI; it pictured a scenario where the former outcome moderately but continuously decreases with increasing recipients' BMI to then sharply decline in the BMI range of 25-35 kg/m2. The miscarriage rate, instead, increases almost linearly with respect to both donors' and recipients' increasing BMI. CONCLUSION: Obesity mostly affects the uterus, especially because of higher miscarriage rates. Yet, poorer outcomes can be appreciated already with a BMI of 25 kg/m2 in both oocyte donors and recipients. Finer markers of nutritional homeostasis are therefore desirable; recipients should be counseled about poorer expected outcomes in cases of overweight and obesity; and oocyte banks should avoid assigning oocytes from overweight donors to overweight and obese recipients.

Major postpartum haemorrhage after frozen embryo transfer: A population-based study.

OBJECTIVE: To investigate the effect on major postpartum haemorrhage (PPH) of mode of conception, differentiating between naturally conceived pregnancies, fresh embryo in vitro fertilisation (fresh-IVF) and frozen embryo transfer (frozen-IVF). DESIGN: Retrospective cohort study. SETTING: The French Burgundy Perinatal Network database, including all deliveries from 2006 to 2020, was linked to the regional blood centre database. POPULATION OR SAMPLE: In all, 244 336 women were included, of whom 240 259 (98.3%) were singleton pregnancies. METHODS: The main analyses were conducted in singleton pregnancies, including 237 608 naturally conceived, 1773 fresh-IVF and 878 frozen-IVF pregnancies. Multivariate logistic regression models adjusted on maternal age, body mass index, smoking, parity, induction of labour, hypertensive disorders, diabetes, placenta praevia and/or accreta, history of caesarean section, mode of delivery, birthweight, birth place and year of delivery, were used. MAIN OUTCOME MEASURES: Major PPH was defined as PPH requiring blood transfusion and/or emergency surgery and/or interventional radiology. RESULTS: The prevalence of major PPH was 0.74% (n = 1749) in naturally conceived pregnancies, 1.92% (n = 34) in fresh-IVF pregnancies, and 3.30% (n = 29) in frozen-IVF pregnancies. The risk of major PPH was higher in frozen-IVF pregnancies than in both naturally conceived pregnancies (adjusted odds ratio [aOR] 2.63, 95% CI 1.68-4.10) and fresh-IVF pregnancies (aOR 2.78, 95% CI 1.44-5.35). CONCLUSIONS: We found that frozen-IVF pregnancies have a higher risk of major PPH and they should be subject to increased vigilance in the delivery room.

Cardiovascular autonomic nervous function in children conceived by assisted reproductive technology with frozen or fresh embryo transfer.

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 ∼17% lower heart rate-corrected standard deviation of normal-to-normal R-R intervals; ∼22% lower heart rate-corrected square root of the mean of the squared difference between successive R-R intervals; and ∼37% 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.

Number of embryos transferred could possibly be associated with angular pregnancy in in vitro fertilization-embryo transfer.

OBJECTIVE: The probability of embryo implantation in an abnormal location is significantly higher in assisted reproductive technology (ART) than in natural pregnancies. Angular pregnancy is an eccentric intrauterine pregnancy with embryo implantation in the lateral superior angle of the uterine cavity. Cycle-level factors associated with angular pregnancy in patients conceived with ART needed to be explored. METHODS: A total of 11 336 clinical pregnancies cycles were included. Angular pregnancy rate was compared among groups according to the type of embryos transferred. Among them, 53 cases of angular pregnancy and 159 cases of normal intrauterine pregnancy were screened out using propensity score matching. Risk factors of angular pregnancy were explored. RESULTS: The angular pregnancy rate was 0.31% (14/4572) in the day 5 blastocyst transfer group, 0.58% (39/6764) in non-day 5 embryo transfer group, with 0.55% (29/5280) in day 3 embryo transfer and 0.67% (10/1484) in the day 6 blastocyst group, respectively. A multifactor regression analysis was performed and indicated that the number of embryos transferred was significantly associated with angular pregnancy (P = 0.031, OR, 2.23, 95% CI: 1.09-4.68). CONCLUSION: Multiple embryo transfer could possibly be associated with an increased incidence of angular pregnancy in patients conceived with ART.

Antibiotic cured chronic endometritis remains a risk factor for early pregnancy loss in the subsequent frozen euploid embryo transfer.

RESEARCH QUESTION: Do patients with antibiotic-cured chronic endometritis (CCE) have a comparable pregnancy outcome to those with non-chronic endometritis (NCE) in the subsequent frozen embryo transfer (FET) cycle? DESIGN: A retrospective cohort analysis included 833 patients in their first FET cycles with single euploid embryo transfer. Chronic endometritis (≥5 CD138+ plasma cells per high-power field [CD138+/HPF]) was treated with standard antibiotic therapy. Patients were classified into two groups: the NCE group (n = 611, <5 CD138+/HPF) and the CCE group (n = 222, ≥5 CD138+/HPF and cured after antibiotic treatment). Pregnancy outcomes were compared. NCE group was divided into subgroup 1 (CD138+/HPF = 0) and subgroup 2 (CD138+/HPF = 1-4) for further analysis. RESULTS: The rate of early pregnancy loss (EPL), incorporating all losses before 10 weeks' gestation, was significantly higher in the CCE group than the NCE group (21.2% versus 14.2%, P = 0.016), and the difference was statistically significant (adjusted odds ratio [AOR] 1.68, 95% confidence interval [CI] 1.11-2.55). No significant differences were observed between the two groups with regard to other pregnancy outcomes. In the subgroup analysis, the EPL rate and biochemical pregnancy rate were significantly higher in subgroup 2 than subgroup 1 (17.2% versus 9.4%, AOR 2.21, 95% CI 1.30-3.74; 12.2% versus 6.9%, AOR 2.01, 95% CI 1.09-3.68). CONCLUSIONS: Chronic endometritis cured by standard antibiotic therapy remains a risk factor for EPL in FET cycles, although no differences were found in live birth rates between patients with CCE or with NCE.

Risk factor for interstitial pregnancy following ipsilateral salpingectomy? A retrospective matched case control study.

BACKGROUND: Interstitial pregnancy may still happen even after ipsilateral salpingectomy, resulting in massive hemorrhage. Therefore, the purpose of the study is to identify risk factors associated with interstitial pregnancy following ipsilateral salpingectomy and discuss possible prevention. METHODS: We conducted a retrospective cohort study in a single, large, university-affiliated hospital. Data of 29 patients diagnosed with interstitial pregnancy following ipsilateral salpingectomy from January 2011 to November 2020 were assigned into the case group (IP group). Whereas there were 6151 patients with intrauterine pregnancy after unilateral salpingectomy in the same period. A sample size of 87 control patients was calculated to achieve statistical power (99.9%) and an α of 0.05. The age, BMI and previous salpingectomy side between the two group were adjusted with PSM at a ratio of 1:3. After PSM, 87 intrauterine pregnancy patients were successfully matched to 29 IP patients. RESULTS: After PSM, parous women were more common and intrauterine operation was more frequent in the IP group compared with control group (P<0.05). There was only one patient undergoing IVF-ET in the IP group as compared with 29 cases in the control group (3.4% vs. 33.3%, P<0.05). Salpingectomy was performed on 5 patients in the IP group and 4 patients in the control group due to hydrosalpinx (P<0.05). Logistic regression indicated that hydrosalpinx was the high risk factor of interstitial pregnancy following ipsilateral salpingectomy (OR = 8.175). CONCLUSIONS: Hydrosalpinx appears to be an independent factor contributing to interstitial pregnancy following ipsilateral salpingectomy in subsequent pregnancy.

Maternal and neonatal complications after IVF/ICSI-fresh embryo transfer in low-prognosis women under the POSEIDON criteria: a retrospective cohort study.

BACKGROUND: Several studies on pregnancy complications of poor ovarian response (POR) patients did not draw a consistent conclusion. The POSEIDON criteria introduces the concept of "low prognosis" and divides POR patients into four groups based on age, AFC and AMH for individualized management. We analyzed low-prognosis population and patients with regular ovarian response, compared maternal and neonatal complications and discussed the relevant risk factors. METHODS: A retrospective cohort study was conducted of females who achieved a singleton clinical pregnancy after IVF / ICSI-fresh embryo transfer in a single center from January 2014 to March 2019. Participants with low prognosis, as defined by the POSEIDON criteria, were enrolled in the study groups. The controls were defined as AFC ≥ five and number of retrieved oocytes > nine. Maternal and neonatal complications were compared among those groups. RESULTS: There were 2554 cycles in POSEIDON group 1, 971 in POSEIDON group 2, 141 in POSEIDON group 3, 142 in POSEIDON group 4, and 3820 in Control. Univariate analysis roughly showed that Groups 2 and 4 had an increased tendency of pregnancy complications. Multi-variable generalized estimating equations (GEE) analysis showed that the risks of GDM, total pregnancy loss, and first-trimester pregnancy loss in Groups 2 and 4 were significantly higher than in Control. The risk of hypertensive disorders of pregnancy (HDP) in Groups 2 and 3 increased, and Group 4 had an increased tendency without statistical significance. After classification by age, GEE analysis showed no significant difference in risks of all complications among groups ≥ 35 years. In patients < 35 years, the risk of HDP in POSEIDON group 3 was significantly higher than in controls (< 35 years), and there was no significant increase in the risk of other complications. CONCLUSION: Compared to patients with regular ovarian response, low-prognosis population have increased tendency of maternal and neonatal complications. In low-prognosis patients, advanced age (≥ 35 years) might be the predominant risk factor for pregnancy complications. In those < 35 years, poor ovarian reserve could contribute to HDP.

Spontaneous unscarred uterine rupture at 13 weeks of gestation after in vitro fertilization-embryo transfer: A case report and literature review.

RATIONALE: Uterine rupture (UR) during pregnancy is a serious obstetric complication. Here we report a case of spontaneous rupture in an unscarred uterus at 13 weeks of gestation after in vitro fertilization embryo transfer, which is not common in past references. Our focus is to understand the relationship between systemic lupus erythematosus (SLE) and UR. PATIENT CONCERNS: A 33-year-old infertile woman with a history of SLE became pregnant after in vitro fertilization embryo transfer. She presented with sudden mental fatigue and dyspnea, accompanied by sweating, dizziness and lower abdominal pain at 13 weeks of gestation. DIAGNOSES: Blood analysis revealed anemia. Ultrasonography and plain computed tomography scan revealed intrauterine early pregnancy with effusion in pelvic and abdominal cavity. Laparotomy confirmed the diagnosis of UR. INTERVENTIONS: The patient underwent emergency laparotomy. Upon surgery, multiple myometrium was weak with only serosal layer visible, and there was a 2.5 cm irregular breach with exposed placenta and villous tissue in the posterior wall of the uterus. After removing intrauterine fetus and repairing the breach, there was still persistent intraperitoneal hemorrhage. The patient underwent subtotal hysterectomy finally. OUTCOMES: Postoperative recovery was uneventful. The patient was discharged on the 8th day after operation. LESSONS: Combined efforts of specialists from ultrasound, imaging and gynecologist led to the successful diagnosis and management of this patient. We should be cautious about the occurrence of unscarred uterus rupture during pregnancy of the women with the disease of SLE and long-term glucocorticoid treatment. In IVF, we had better transfer one embryo for these patients with the history of SLE. Obstetricians should strengthen labor tests to detect early signs of UR of the patients with SLE and long term glucocorticoid treatment. Once UR is suspected, prompt surgical treatment is needed as soon as possible.