Analysis of factors influencing pregnancy and its outcomes in women undergoing in vitro fertilization-embryo transfer/frozen embryo transfer cycles: A retrospective study.

The relationship between clinical outcomes and various factors influencing pregnancy was analyzed to provide reference data for patients and clinicians when selecting embryo transfer protocols. This was a retrospective study of 1309 transfer cycles between June 1, 2018, and May 1, 2023, in the Reproductive Medicine Center. Univariate analysis was performed on various factors that may have affected pregnancy outcomes, and further regression analysis was performed on those factors found by univariate analysis to correlate positively with clinical pregnancy outcomes. Finally, the embryo transfer schemes were compared based on the analysis results. The results showed that the stage of embryonic development significantly affected pregnancy outcomes after transplantation (P < .01, 95% confidence interval: 2.554 [1.958-3.332]). There was no significant difference in the pregnancy rate between 1 high-quality blastocyst transfer and 2 cleavage-stage embryos or blastocyst transfer (64.22% vs 70.11%, P = .439); however, the rate of multiple pregnancies after 1 high-quality blastocyst transfer was close to the rate of natural conception. These data show that the transfer of single high-quality blastocysts can significantly reduce the multiple pregnancy rate while ensuring an ideal pregnancy rate, which can be used as a reference for planning the first transplantation in patients with good prognoses.

Clinical data-based modeling of IVF live birth outcome and its application.

BACKGROUND: The low live birth rate and difficult decision-making of the in vitro fertilization (IVF) treatment regimen bring great trouble to patients and clinicians. Based on the retrospective clinical data of patients undergoing the IVF cycle, this study aims to establish classification models for predicting live birth outcome (LBO) with machine learning methods. METHODS: The historical data of a total of 1405 patients undergoing IVF cycle were first collected and then analyzed by univariate and multivariate analysis. The statistically significant factors were identified and taken as input to build the artificial neural network (ANN) model and supporting vector machine (SVM) model for predicting the LBO. By comparing the model performance, the one with better results was selected as the final prediction model and applied in real clinical applications. RESULTS: Univariate and multivariate analysis shows that 7 factors were closely related to the LBO (with P < 0.05): Age, ovarian sensitivity index (OSI), controlled ovarian stimulation (COS) treatment regimen, Gn starting dose, endometrial thickness on human chorionic gonadotrophin (HCG) day, Progesterone (P) value on HCG day, and embryo transfer strategy. By taking the 7 factors as input, the ANN-based and SVM-based LBO models were established, yielding good prediction performance. Compared with the ANN model, the SVM model performs much better and was selected as the final model for the LBO prediction. In real clinical applications, the proposed ANN-based LBO model can predict the LBO with good performance and recommend the embryo transfer strategy of potential good LBO. CONCLUSIONS: The proposed model involving all essential IVF treatment factors can accurately predict LBO. It can provide objective and scientific assistance to clinicians for customizing the IVF treatment strategy like the embryo transfer strategy.

Comparison of pregnancy outcomes between 4th day morula and 5th day blastocyst after embryo transfer: a retrospective cohort study.

BACKGROUND: This study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5). METHODS: From September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes. RESULTS: In single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P < 0.05). The preterm delivery rate, twin delivery rate, cesarean delivery rate, and percentage of low birthweight infants were lower in the D5A group than in the D5B group (P < 0.05). Analysis of factors influencing live birth outcomes further confirmed the absence of a significant difference between D4 and D5 transplantation in achieving live birth (P > 0.05). CONCLUSION: When factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.

Ongoing pregnancy rates in single euploid frozen embryo transfers remain unaffected by female age: a retrospective study.

RESEARCH QUESTION: Is female age a significant factor in the likelihood of an ongoing pregnancy in single euploid frozen embryo transfers (FET)? DESIGN: Retrospective study of 1923 single euploid FET cycles in 1464 women, either in a natural cycle or a hormone replacement therapy cycle. The primary outcome was the ongoing pregnancy rate (OPR). RESULTS: There were 990 (51.48%) ongoing pregnancies among 1923 included transfers. The OPR were 51.4%, 49.1%, 53.3% and 52.3% for women aged ≤35, >35-≤37, >37-≤40 and >40 years at oocyte retrieval (OCR), without a significant trend for decreasing OPR (P = 0.679). No significant differences in female age at embryo transfer (P = 0.609) and female age at OCR (P = 0.816) were found between the groups (ongoing pregnancy versus no pregnancy or miscarriage). Women who received good-quality embryos (P < 0.001), had a lower body mass index (BMI) (P < 0.001), had achieved at least one pregnancy previously (P < 0.001), and underwent natural cycle endometrial preparation (P < 0.001) were more likely to achieve an ongoing pregnancy. Multivariable regression analysis (adjusted for BMI, embryo quality and endometrial preparation) did not show a significant effect of female age at OCR on achieving an ongoing pregnancy. Compared with women aged ≤35 years, none of the age groups had significantly higher or lower OPR. A multinomial regression analysis showed that BMI, embryo quality and endometrial preparation were associated with miscarriage/no pregnancy versus ongoing pregnancy (P = 0.001, 0.001 and 0.001, respectively). Female age had no significant association with either outcome. CONCLUSIONS: Female age in itself does not have a substantial impact on the OPR in single euploid FET cycles, but the OPR is impacted significantly by embryo quality, BMI, previous parity, and a natural cycle endometrial preparation protocol.

The role of age and AMH on cumulative live birth rates over multiple frozen-thawed embryo transfer cycles: a study based on low prognosis patients of POSEIDON 3 and 4 groups.

BACKGROUND: Among the POSEIDON criteria, group 3 and group 4 have an expected low prognosis. For those patients with inadequate ovary reserve, embryo accumulated from consecutive oocyte retrieval cycles for multiple frozen-thawed embryo transfers (FET) has become more common. It is necessary to inform them of the pregnancy outcomes after single or multiple FET cycles before the treatment. However few studies about cumulative live birth rate (CLBR) for those with low prognosis have been reported. METHODS: This retrospective study included 4712 patients undergoing frozen embryo transfer cycles from July 2015 to August 2020. Patients were stratified as POSEIDON group 3, group 4, control 1 group (< 35 years) and control 2 group (≥ 35 years). The primary outcome is CLBRs up to six FET cycles and the secondary outcomes were LBRs per transfer cycle. Optimistic approach was used for the analysis of CLBRs and the depiction of cumulative incidence curves. RESULTS: Under optimistic model analyses, control 1 group exhibited the highest CLBR (93.98%, 95%CI 91.63-95.67%) within 6 FET cycles, followed by the CLBR from women in POSEIDON group 3(92.51%, 95%CI 77.1-97.55)was slightly lower than that in control 1 group. The CLBR of POSEIDON group 4(55% ,95%CI 39.34-70.66%)was the lowest and significantly lower than that of control 2 group(88.7%, 95%CI 80.68-96.72%). Further, patients in POSEIDON group 4 reached a CLBR plateau after 5 FET cycles. CONCLUSIONS: The patients of POSEIDON group 3 may not be considered as traditional "low prognosis" in clinical practice as extending the number of FET cycles up to 6 can archive considerably CLBR as control women. While for the POSEIDON group 4, a simple repeat of the FET cycle is not recommended after four failed FET cycles, some strategies such as PGT-A may be beneficial.

Influence of COVID-19 infection on early pregnancy outcomes in different periods around frozen embryo transfer.

PURPOSE: The study aimed to investigate the potential influence of COVID-19 infection on embryo implantation and early development in women undergoing frozen embryo transfer (FET), with a specific focus on infections occurring at different periods around FET. METHODS: A retrospective analysis was performed on women who had undergone FET during a period marked by a significant surge in COVID-19 infection in Shanghai. All enrolled women experienced their first documented COVID-19 infection around the time of FET, ensuring that infections did not occur prior to oocyte retrieval. Participants were categorized into six groups based on the timing of infection: uninfected, ≥ 60 days, < 60 days before FET, 0-14 days, 15-28 days, and 29-70 days after FET. Clinical outcomes were compared across these groups. RESULTS: The infection rate among the total of 709 cases was 78.28%. Infected individuals exhibited either asymptomatic or mild symptoms. The ongoing pregnancy rates for the first four groups were 40.7%, 44.4%, 40.5%, and 34.2% (P = 0.709) respectively, biochemical pregnancy rates (59.1% vs. 61.1% vs. 67.6% vs. 55.7%, P = 0.471) and clinical pregnancy rates (49.6% vs. 55.6% vs. 55.4% vs. 48.1%, P = 0.749), all showed no significant differences. Early spontaneous abortion rates across all six groups were 18.3%, 20.0%, 25.0%, 28.9%, 5.4%, and 19.0% respectively, with no significant differences (P = 0.113). Multivariable logistic analysis revealed no significant correlation between the infection and ongoing pregnancy. CONCLUSION: Asymptomatic or mild COVID-19 infections occurring around FET do not appear to have a significant adverse impact on early pregnancy outcomes.

Medically Assisted Reproduction and Risk of Cancer Among Offspring.

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 8 526 306 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 260 236 children (3.1%) born after MAR, including 133 965 (1.6%) after fresh ET, 66 165 (0.8%) after FET, and 60 106 (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.

Mild obesity does not affect perinatal outcome in gestational carrier cycles.

STUDY QUESTION: Does BMI of gestational carriers (GCs) affect perinatal outcomes after embryo transfer? SUMMARY ANSWER: Overweight and class I obesity in GCs does not affect the rate of good perinatal outcomes. WHAT IS KNOWN ALREADY: The use of GCs is increasing, but uniform guidance regarding optimal BMI for GCs is lacking. Women with obesity who conceive without fertility treatment or through autologous or donor in vitro fertilization are at higher risk of adverse maternal and fetal outcomes, but data on obesity in GCs are very limited. STUDY DESIGN, SIZE, DURATION: We performed a retrospective cohort study of 1121 GC cycles from January 2015 to December 2020 at US Fertility, the largest national partnership of fertility practices in the USA. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: All GC cycles performed at a large network of fertility practices were reviewed. Same-sex partners undergoing co-IVF were excluded. The primary outcome was good perinatal outcome from the first embryo transfer, defined as a singleton live birth at ≥37 weeks of gestation with birth weight between 2500 and 4000 g. Secondary outcome measures included frequencies of live birth, clinical pregnancy, miscarriage, full-term birth, low birth weight, large for gestational age, and cesarean delivery. A generalized linear model (log-binomial) was used for each to compare outcomes across BMI groups using normal BMI (20-24.9 kg/m2) as the reference group. Risk ratios and 95% CIs were estimated for each category group relative to normal BMI. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 1121 cycles in which GCs underwent first embryo transfer, of which 263 (23.5%) were in GCs with BMI >30. Demographics and reproductive history for GCs did not differ by BMI groups. The age of intended parents, use of frozen eggs, and fresh embryo transfers were higher with increasing BMI group. There were no statistically significant associations between BMI and good perinatal outcomes, live birth, clinical pregnancy, biochemical, spontaneous abortion, or low birth weight. However, among live births, higher BMI was significantly associated with birth by cesarean (P = 0.015) and large for gestational age infants (P = 0.023). LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study, and there may be unmeasured confounders. The number of patients with BMI <20 or ≥35 was small, limiting the power for these groups. We were not able to assess all maternal and fetal outcomes. WIDER IMPLICATIONS OF THE FINDINGS: In this study, we did not identify any significant impact of BMI on the chances of having a good perinatal outcome. Prior research studies have been inconsistent and this is the largest study to date. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this work. The authors do not have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Does recurrent implantation failure exist? Prevalence and outcomes of five consecutive euploid blastocyst transfers in 123 987 patients.

STUDY QUESTION: What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures in the absence of another known factor that affects implantation? SUMMARY ANSWER: The fourth and fifth euploid blastocyst transfers resulted in similar live birth rates of 40% and 53.3%, respectively, culminating in a cumulative live birth rate of 98.1% (95% CI = 96.5-99.6%) after five euploid blastocyst transfers. WHAT IS KNOWN ALREADY: The first three euploid blastocysts have similar implantation and live birth rates and provide a cumulative live birth rate of 92.6%. STUDY DESIGN, SIZE, DURATION: An international multi-center retrospective study was conducted at 25 individual clinics. The study period spanned between January 2012 and December 2022. A total of 123 987 patients with a total of 64 572 euploid blastocyst transfers were screened for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with a history of any embryo transfer at another clinic, history of any unscreened embryo transfer at participating clinics, parental karyotype abnormalities, the use of donor oocytes or a gestational carrier, untreated intracavitary uterine pathology (e.g. polyp, leiomyoma), congenital uterine anomalies, adenomyosis, communicating hydrosalpinx, endometrial thickness <6 mm prior to initiating of progesterone, use of testicular sperm due to non-obstructive azoospermia in the male partner, transfer of an embryo with a reported intermediate chromosome copy number (i.e. mosaic), preimplantation genetic testing cycles for monogenic disorders, or structural chromosome rearrangements were excluded. Ovarian stimulation protocols and embryology laboratory procedures including trophectoderm biopsy followed the usual practice of each center. The ploidy status of blastocysts was determined with comprehensive chromosome screening. Endometrial preparation protocols followed the usual practice of participating centers and included programmed cycles, natural or modified natural cycles. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 105 (0.085% of the total population) patients met the criteria and underwent at least one additional euploid blastocyst transfer after failing to achieve a positive pregnancy test with three consecutive euploid blastocyst transfers. Outcomes of the fourth and fifth euploid blastocyst transfers were similar across participating centers. Overall, the live birth rate was similar with the fourth and fifth euploid blastocysts (40% vs 53.3%, relative risk = 1.33, 95% CI = 0.93-1.9, P value = 0.14). Sensitivity analyses excluding blastocysts biopsied on Day 7 postfertilization, women with a BMI >30 kg/m2, cycles using non-ejaculate or donor sperm, double-embryo transfer cycles, and cycles in which the day of embryo transfer was modified due to endometrial receptivity assay test result yielded similar results. Where data were available, the fourth euploid blastocyst had similar live birth rate with the first one (relative risk = 0.84, 95% CI = 0.58-1.21, P = 0.29). The cumulative live birth rate after five euploid blastocyst transfers was 98.1% (95% CI = 96.5-99.6%). LIMITATIONS, REASONS FOR CAUTION: Retrospective design has its own inherent limitations. Patients continuing with a further euploid embryo transfer and patients dropping out from treatment after three failed euploid transfers can be systematically different, perhaps with regard to ovarian reserve or economic status. WIDER IMPLICATION OF THE FINDINGS: Implantation failure seems to be mainly due to embryonic factors. Given the stable and high live birth rates up to five euploid blastocysts, unexplained recurrent implantation failure should have a prevalence of <2%. Proceeding with another embryo transfer can be the best next step once a known etiology for implantation failure is ruled out. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Fetal growth after fresh and frozen embryo transfer and natural conception: A population-based register study.

OBJECTIVE: To investigate fetal growth trajectories and risks of small and large for gestational age (SGA and LGA), and macrosomia in pregnancies after fresh and frozen embryo transfer (ET), and natural conception (NC). DESIGN: Longitudinal population-based cohort study. SETTING: Swedish national registers. POPULATION: A total of 196 008 singleton pregnancies between 2013 and 2017. METHODS: Of all singleton pregnancies resulting in live births in the Swedish Pregnancy Register, 10 970 fresh ET, 6520 frozen ET, and 178 518 NC pregnancies with ultrasound data were included. A general least squares model was used to examine the effect of fresh or frozen ET on fetal growth while adjusting for confounders. MAIN OUTCOME MEASURES: Fetal growth velocity. SGA, LGA and macrosomia. RESULTS: At 120 days, fetal weights were lower in fresh ET pregnancies compared with NC pregnancies. Thereafter fresh ET as well as FET fetuses had higher fetal weights than NC fetuses, with no differences between themselves until the second trimester. From 210 days, FET fetuses were heavier than fresh ET fetuses, whereas fresh ET fetuses had lower fetal weights than NC fetuses from 245 days. After fresh ET, SGA was more frequent, whereas LGA and macrosomia were less frequent, than after FET. CONCLUSIONS: This study gives new insights into the differences in fetal growth dynamics between fresh and frozen ET and NC pregnancies. Clinically relevant differences in proportions of SGA, LGA and macrosomia were observed.

Association of duration of embryo culture with risk of large for gestational age delivery in cryopreserved embryo transfer cycles.

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.

Cumulative live birth rates for low-prognosis women over 5 years or 9 frozen-thawed embryo transfer cycles.

BACKGROUND: For heterogeneous populations of low-prognosis women, it remains unclear as to how long individuals should continue undergoing ART when attempting to have a baby, as there have been insufficient studies to date tracking the cumulative live birth rates (CLBRs) for these women over the entire course of their ART treatment, particularly over extended time periods. METHODS: This was a retrospective analysis of 17,698 women at a tertiary care academic medical center who had begun undergoing IVI/ICSI cycles using a progestin-primed ovarian stimulation (PPOS) approach between January 2013 and January 2019. Low-prognosis patients were stratified into four groups based upon POSEIDON criteria, with patients exhibiting normal or high ovarian reserves and response to stimulation (defined as AFC ≥5, > 9 oocytes retrieved) being included as controls (group 5). The CLBR within 5 years or 9 FET cycles from the ovum pick-up (OPU) day of the first cycle was the primary endpoint for this study, including all repetitive oocyte retrieval cycles and subsequent FET cycles. Optimistic and conservative approaches were used for the analysis of CLBRs and the depiction of cumulative incidence curves. RESULTS: Under both optimistic and conservative model analyses, normal and good responders exhibited the highest CLBR within 5 years or 9 FET cycles, followed by younger unexpected poor responders, younger expected poor responders, older unexpected poor responders, and older expected poor responders. Upward trends in CLBRs were evident across the five groups with the prolongation of time or an increase in FET cycle counts. Within the first 2 years or 3 FET cycles, the CLBRs rose rapidly, followed by more moderate increases over the following 2-3.5 years or 4-6 cycles, with expected poor responders exhibiting the most obvious improvements. All Patients reached a CLBR plateau after 3.5 years or 6 FET cycles. CONCLUSIONS: All low-prognosis women should undergo ART treatment for a minimum of 2 years or 3 FET cycles, and exhibit better outcomes when extending ART treatment to 3.5 years or 6 FET cycles (particularly for POSEIDON groups 3 and 4), but should consider ceasing further treatment thereafter due to a lack of apparent benefit.

Effect of previous wedge resection for interstitial pregnancy on pregnancy and neonatal outcomes following frozen-thawed embryo transfer (FET) cycles of IVF/ICSI: a retrospective study.

OBJECTIVE: The present study aimed to evaluate pregnancy and neonatal outcomes in women, with a previous history of wedge resection for interstitial pregnancy, in frozen-thawed embryo transfer (FET) cycles of IVF/ICSI. METHODS: The present study involved a retrospective case-control assessment of 75 cases and 375 control subjects over 6 years in a single center. To compare pregnancy and neonatal outcomes between cases, treated using wedge resection, and controls without any previous history of ectopic pregnancy, propensity score matching (1:5) was utilized. The study also compared subgroups in the case group. RESULTS: Women with previous wedge resection exhibited higher rates of ectopic pregnancy and uterine rupture rate as compared to control subjects (9.1% vs 1.3%, P = 0.025 and 4.5% vs 0%, P = 0.035, respectively). No statistically significant differences were recorded between the two cohorts with regard to clinical pregnancy rate, live birth rate, and neonatal outcomes. For pregnancy type subgroup analysis, Z-score and rates of large for gestational age were recorded to be significantly lower in twin pregnancy subgroup when compared with singleton pregnancy subgroup (0.10 (- 0.59, 0.25) vs 0.50 (- 0.97, 1.39), P = 0.005; 4.5% vs 26.1%, P = 0.047, respectively). CONCLUSION: The results of the present study indicated that previous wedge resection correlated to a higher risk of ectopic pregnancy and uterine rupture. However, it might not be related to an increased risk of adverse neonatal outcomes. The study recommended cesarean section in these patients. Further studies are required to verify the validity of current recommendations.

Sex ratio imbalance following blastocyst transfer is associated with ICSI but not with IVF: an analysis of 14,892 single embryo transfer cycles.

PURPOSE: Assisted reproductive technology (ART) has an impact on secondary sex ratio (SSR), which is seemed to be elevated after blastocyst transfer (BT) but decreased following ICSI procedure. We aim to assess whether the higher SSR associated with BT could be influenced by fertilization method used. METHODS: All consecutive IVF/ICSI cycles (fresh and frozen) involving single embryo transfer (SET) resulting in a live birth between 2015 and 2019 were retrospective analyzed. Logistic regression was used to model the effect on the SSR of maternal and specific ART characteristics. RESULTS: Six thousand nine hundred twenty-two women were included with the crude SSR of 54.8%. The impact of BT on SSR is influenced by the fertilization method used. After adjustment for potential confounders, the SSR in the ICSI BT group was significantly higher when compared to ICSI cleavage-stage embryo SET (aOR 1.24; 95% CI 1.10-1.40, P < 0.001). However, this effect was not detected among SBT with IVF treatment (aOR 1.04; 95% CI 0.97-1.12, P = 0.260). Assessing blastocyst morphological parameters, high trophectoderm quality was significantly associated with elevated SSR (aOR 1.76, 95% CI 1.34-2.31 [A vs. C], and aOR 1.28, 95% CI 1.14-1.44 [B vs. C]). No significant difference was shown in expansion, inner cell mass, or days of blastocyst formation between male and female blastocysts. CONCLUSIONS: The impact of BT on SSR could be influenced by the fertilization method used. The higher SSR was observed after BT with ICSI procedures but not with IVF. Interpretation of the findings is limited by the potential for selection and confounding bias.

Effects of the Zishen Yutai Pill Compared With Placebo on Live Births Among Women in a Fresh Embryo Transfer Cycle: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of the Zishen Yutai Pill compared with placebo on live birth rates among women after fresh embryo transfer cycles. METHODS: We conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of the Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer after in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate. Secondary outcomes were rates of implantation, biochemical pregnancy, clinical pregnancy, pregnancy loss, cycle cancellation, and maternal, fetal, and neonatal complications. A total sample size of 2,265 women (1:1 in two groups) was used to detect a live birth rate difference between the Zishen Yutai Pill and placebo. Participants were enrolled and randomized to receive 5 g of the Zishen Yutai Pill or placebo orally, three times per day during the study. RESULTS: Recruitment was completed between April 2014 and June 2017, with 2,580 patients screened. Two thousand two hundred sixty-five patients were randomized: 1,131 to the Zishen Yutai Pill and 1,134 to placebo. Characteristics were similar between groups. In intention-to-treat analysis, the rates of live birth in the Zishen Yutai Pill (ZYP) group and placebo group were 26.8% and 23.0% (rate ratio [RR], 1.16; 95% CI 1.01-1.34; P=.038), respectively. The implantation rates were 36.8% and 32.6% in the ZYP and placebo groups, respectively (RR 1.13; 95% CI 1.01-1.25; P=.027). The biochemical pregnancy rate for the ZYP group was 35.5% compared with 31.1% in the placebo group (RR 1.14; 95% CI 1.02-1.28; P=.026). The rates of clinical pregnancy in the ZYP and placebo groups were 31.2% compared with 27.3%, respectively (RR 1.14; 95% CI 1.00-1.30; P=.043). There were no significant between-group differences in the rates of pregnancy loss, maternal, or neonatal complications (all P>.05). CONCLUSION: The Zishen Yutai Pill increased the rate of live birth after fresh embryo transfer compared with placebo. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, Chictr-TRC-14004494.

Informative predictors of pregnancy after first IVF cycle using eIVF practice highway electronic health records.

The aim of this study is to determine the most informative pre- and in-cycle variables for predicting success for a first autologous oocyte in-vitro fertilization (IVF) cycle. This is a retrospective study using 22,413 first autologous oocyte IVF cycles from 2001 to 2018. Models were developed to predict pregnancy following an IVF cycle with a fresh embryo transfer. The importance of each variable was determined by its coefficient in a logistic regression model and the prediction accuracy based on different variable sets was reported. The area under the receiver operating characteristic curve (AUC) on a validation patient cohort was the metric for prediction accuracy. Three factors were found to be of importance when predicting IVF success: age in three groups (38-40, 41-42, and above 42 years old), number of transferred embryos, and number of cryopreserved embryos. For predicting first-cycle IVF pregnancy using all available variables, the predictive model achieved an AUC of 68% + /- 0.01%. A parsimonious predictive model utilizing age (38-40, 41-42, and above 42 years old), number of transferred embryos, and number of cryopreserved embryos achieved an AUC of 65% + /- 0.01%. The proposed models accurately predict a single IVF cycle pregnancy outcome and identify important predictive variables associated with the outcome. These models are limited to predicting pregnancy immediately after the IVF cycle and not live birth. These models do not include indicators of multiple gestation and are not intended for clinical application.

Embryo attrition in planned PGT-A: predicting the number of available blastocysts for transfer.

PURPOSE: During a typical IVF cycle, there is unavoidable attrition from oocytes retrieved to blastocysts formed. Some patients will not have blastocysts available to biopsy or embryos for transfer. The purpose of this study was to predict the number of transferable blastocysts available for patients based on their age and number of 2pn zygotes. METHODS: This was a retrospective cohort study of all fresh autologous IVF and ICSI cycles in which PGT-A was planned from 1/2012 to 3/2020. In total, 746 cycles from 571 patients were analyzed. Patient cycles were stratified into two groups: less than four 2pn zygotes (n = 85) and at least four 2pn zygotes (n = 661). Cycles were then stratified by patient age. Cycle outcomes, including number of cleavage-stage embryos, blastocysts, euploid blastocysts, and low level mosaic blastocysts, were determined. RESULTS: Cleavage-rate was independent of age and number of 2pn zygotes and ranged between 96 and 100%. Blastocyst conversion and euploid blastocyst conversion rates were directly correlated to age, ranging from 52 to 83% for blastocyst conversion and 0-28% for euploid blastocyst conversion. For patients above the age of 40 years with less than four 2pn zygotes, the risk of having no transferable embryos was 99.7%. CONCLUSION: While the literature demonstrates higher live birth rates with the use of PGT-A in women of advancing age, this is inconsequential if there is no embryo available to transfer. Women over 40 years with less than four 2pn zygotes should consider transfer of one or more untested embryos either on day 3 or on day 5.

Retrospective comparison of pregnancy outcomes of fresh and frozen-warmed single blastocyst transfer: a 5-year single-center experience.

PURPOSE: To assess whether live birth rates (LBR) and maternal/neonatal complications differed following single fresh and frozen-warmed blastocyst transfer. METHODS: The present retrospective observational study analyzed 4,613 single embryo transfers (SET) (646 fresh and 3,967 frozen) from January 1, 2014, to December 31, 2018. Fresh embryo transfer at blastocyst stage was considered according to the age of the patient and her prognosis. In case of the risk of ovarian hyperstimulation syndrome, premature progesterone rise, non-optimal endometrial growth, or supernumerary embryos, cryopreservation with subsequent frozen embryo transfer (FET) was indicated. RESULTS: No differences in LBR were recorded. Fresh embryo transfers yielded an increase both in neonatal complications OR 2.15 (95% CI 1.20-3.86, p 0.010), with a higher prevalence of singletons weighting below the 5th percentile (p 0.013) and of intrauterine growth retardation (p 0.015), as well as maternal complications, with a higher placenta previa occurrence OR 3.58 (95% CI 1.54-8.28, p 0.003), compared to FET. CONCLUSION: LBR appears not to be affected by the transfer procedure preferred. Fresh embryo transfer is associated with higher risk of neonatal complications (specifically a higher prevalence of singletons weighting below the 5th percentile and of intrauterine growth retardation) and placenta previa. Reflecting on the increased practice of ART procedures, it is imperative to understand whether a transfer procedure yields less complications than the other and if it is time to switch to a "freeze-all" procedure as standard practice. TRIAL REGISTRATION: Clinical Trial Registration Number: NCT04310761. Date of registration: March 17, 2020, retrospectively registered.

Impact of body mass index (BMI) on the success rate of fresh embryo transfer in women undergoing first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.

OBJECTIVE: To investigate the impact of body mass index (BMI) on the success rate and prenatal outcomes of fresh embryo transfer in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. METHODS: It is a post-hoc analysis of a prospective observational cohort study. 2569 Chinese women were grouped in quintiles of BMI and according to the official Chinese classification of body weight. IVF/ICSI and pregnancy outcomes were compared between groups. RESULTS: BMI was not associated with IVF/ICSI pregnancy outcomes including hCG positive rate, clinical pregnancy rate, implantation rate, ectopic pregnancy rate, ongoing pregnancy rate, early miscarriage rate, and live birth rate. However, it was negatively related to some pregnancy complications such as gestational diabetes mellitus (GDM) and hypertension. Additionally, the proportion of Cesarean-section was increased with BMI. As for prenatal outcomes, the current results showed no statistical difference in the number of male and female newborn, the proportion of low live birth weight (<2500 g), macrosomia (≥4000 g) (both in all live birth and full-term live birth), and premature delivery (<37 weeks). CONCLUSIONS: The current study showed that BMI was not associated with embryo transfer outcomes after fresh embryo transfer in women undergoing their first IVF/ICSI treatment, whereas BMI was associated with GDM and gestational hypertension.

Outcomes of embryo transfers performed by Reproductive Endocrinology and Infertility fellows vs. faculty: an 11-year retrospective review.

OBJECTIVE: To compare the clinical pregnancy rate (CPR) and live birth rate (LBR) of embryo transfer episodes (ETEs) performed by Reproductive Endocrinology and Infertility fellows vs. those of ETEs performed by faculty physicians. DESIGN: Retrospective cohort analysis. SETTING: Academic reproductive endocrinology and infertility practice. PATIENT(S): In total, 3,073 ETEs for 1,488 unique patients were performed by fellows or faculty physicians between January 2009 and January 2020. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate and LBR. RESULT(S): Fifteen fellows performed 1,225 (39.9%) of 3,073 ETEs after completing 30 mock transfers. On comparing outcomes among fellowship years (FY1, FY2, and FY3), CPR (44.1% vs. 43.2% vs. 45.7%, respectively, P = .83) and LBR (39.1% vs. 38.1% vs. 38.4%, respectively, P = .97) were not significantly different. Fellowship year 1 fellows' initial 30 ETEs vs. all the remaining FY1 ETEs had a significantly higher CPR (48.1% vs. 40.5%, respectively, P = .030) and LBR (45.4% vs. 34.3%, respectively, P = .001). There were no significant differences between faculty versus fellow ETEs in terms of CPR (43.0% vs. 45.0%, respectively, P = .30) or LBR (37.3% vs. 39.8%, respectively, P = .16), even after adjusting for patient age, body mass index, primary infertility diagnosis, autologous vs. donor oocyte, fresh vs. frozen embryo, number of embryos transferred, type of transfer catheter, and year of transfer (P = .32 for CPR, P = .22 for LBR). CONCLUSION(S): Appropriately trained FY1 fellows had success rates maintained throughout all FYs. There were no significant differences in clinical outcomes between fellow- and faculty-performed transfers. These data demonstrated that allowing fellows to perform live embryo transfers is not detrimental to clinical outcomes.