Reproductive Technology Clinic Outcome Reporting Research Articles

Protocol change improves live birth and recurrent cycle cancellation rates after a previous IVF cycle cancellation: an analysis of 13000 autologous cycles reported to SART CORS.

After an IVF cycle cancellation, does changing the stimulation protocol affect the odds of live birth and recurrent cancellation in the subsequent cycle? After IVF cycle cancellation, compared to those who repeated the same stimulation protocol, those who changed their protocol had higher odds of live birth and lower odds of recurrent cycle cancellation. There is limited data addressing the effect of changing the stimulation protocol after an IVF cycle is cancelled during initial stimulation. The odds of live birth outcomes are not known so far in studies addressing the effect of changing the protocol. Retrospective Cohort Study using the 2014-2017 Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database. The data included 13135 patients with a first autologous IVF cycle that resulted in a cycle cancellation and was followed by a second autologous cycle within the study period. We excluded fertility preservation cycles, supernumerary cycle attempts after the second IVF cycle attempt, and cycles with more than one stimulation protocol documented per cycle start. Patients who received the same protocol for both cycles (n = 6434) were compared to those who changed their protocol in the second cycle (n = 6701). Multivariable logistic regression analyses were performed to estimate the adjusted odds of live birth and recurrent cancellation. Changing the protocol in the second cycle resulted 14% lower odds of recurrent cycle cancellation (P = 0.01) and 17% higher odds of live birth after fresh transfers (P = 0.04). When stratifying the data by specific combinations of protocol change (agonist flare, agonist suppression, antagonist), there was an increase in live birth when switching from antagonist to agonist suppression (odds ratio (OR) = 1.36, P = 0.03) and from agonist suppression to antagonist (OR = 1.73, P = 0.01) compared to those who repeated their same stimulation protocol. Specifically in poor responders, outcomes were worse when using the agonist flare protocol and significantly improved with the agonist suppression protocol. Comparison of response to stimulation between first and second cycles cannot be made in this study because the index IVF cycle was cancelled during ovarian stimulation, and thus there is no reportable outcome data for that cycle. Additionally, SART only tracks the three stimulation protocols addressed in this study and does not have data on more contemporary protocols that are used in poor responders thus limiting the generalizability of our findings. Using the SART CORS database, which includes >90% of all reported IVF cycles in the USA, provides generalizability to the demographically diverse IVF populations found here. In agreement with prior studies assessing change in IVF protocols, the agonist flare protocol seems to result in worse IVF outcomes, and based on our results, we believe that there is no role for the agonist flare protocol in patients with a prior poor response to stimulation. None declared. N/A.

Assessment of a Decade of Change in U.S. Assisted Reproductive Technology Cumulative Live-Birth Rates: 2004-2009 Compared With 2014-2020.

To assess the effects of demographic shifts, changes in contemporaneous clinical practices, and technologic innovation on assisted reproductive technology (ART) success rates by conducting an analysis of cumulative live-birth rates across different time periods, age groups, and infertility diagnoses. We conducted a retrospective cohort study of autologous linked cycles comparing cumulative live-birth rates over successive cycles from patients undergoing their first retrieval between 2014 and 2019 in the SART CORS (Society for Assisted Reproductive Technology Clinic Outcome Reporting System) database. All cycles reported for these individuals up to 2020 were included for analysis. We compared cumulative live-birth rates stratified by age and infertility cause with published data from the 2004-2009 SART CORS database. From 2014 to 2019, 447,042 patients underwent their first autologous index retrieval, resulting in 1,007,374 cycles and 252,215 live births over the period of 2014 to 2020. In contrast, between 2004 and 2008, 246,740 patients underwent 471,208 cycles, resulting in 140,859 births by 2009. Noteworthy shifts in demographics were observed, with an increase in people of color seeking reproductive technology (57.9% vs 51.7%, P<.001). There was also an increase in patients with diminished ovarian reserve and ovulatory disorders and a decrease in endometriosis, tubal, and male factor infertility (P<.001). Previously associated with decreased odds of live birth, frozen embryo transfer and preimplantation genetic testing showed increased odds in 2014-2020. Preimplantation genetic testing rose from 3.4% to 36.0% and was associated with a lower cumulative live-birth rate for those younger than age 35 years (P<.001) but a higher cumulative live-birth rate for those aged 35 years or older (P<.001). Comparing 2014-2020 with 2004-2009 shows that the overall cumulative live-birth rate improved for patients aged 35 years or older and for all infertility diagnoses except ovulatory disorders (P<.001). This analysis provides insights into the changing landscape of ART treatments in the United States over the past two decades. The observed shifts in demographics, clinical practices, and technology highlight the dynamic nature of an evolving field of reproductive medicine. These findings may offer insight for clinicians to consider in counseling patients and to inform future research endeavors in the field of ART.

U.S. Gestational Carrier Embryo Transfer Trends, 2014–2020 [ID 2683526

INTRODUCTION: Multiple embryo transfers (METs) are common among gestational carriers (GCs) despite increased obstetric risks of multiple gestations and strong recommendations from American Society for Reproductive Medicine (ASRM) for single-embryo transfers. This study assessed GC embryo transfer trends from 2014–2020 to evaluate compliance with national guidelines. METHODS: This retrospective, population-based cohort study used data from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. All cycles from 2014 to 2020 involving an embryo transfer to a GC were analyzed. The number of GC embryo transfers, use of preimplantation genetic testing (PGT), and outcome (singleton versus multiple gestation) were assessed. Poisson and linear regression models evaluated trends in number and proportion of cycles over time. Institutional review board approval was obtained. RESULTS: Of the 40,177 GC transfer cycles from 2014 to 2020, 11,081 (27.6%) involved transfer of two or more embryos. Both the number (n=2,001 in 2014; n=814 in 2020) and proportion of METs (56.6% of all transfers in 2014; 11.8% in 2020) (P&lt;.05 for both) decreased. The use of PGT among MET GC cycles increased from 23.9% in 2014 to 61.4% in 2020. Among live births, there was a 71.0% reduction in the proportion of multiple gestations from 2014 (25.5%) to 2020 (7.4%) (P&lt;.05). Among double-embryo transfers, the majority were performed at the blastocyst stage with an increase from 2014 (76.7%) to 2020 (88.1%) (P&lt;.05). CONCLUSION: With increased use of PGT and extended blastocyst culture, MET and subsequent multiple gestation pregnancies have decreased amongst U.S. GCs. These trends suggest increased compliance with ASRM national guidelines.

An Investigation of Racial and Ethnic Disparities in Donor Sperm Availability in the United States

To determine whether the racial and ethnic distribution of sperm donors contributing to United States (US) sperm banks differ from the demographics of the US population and those of US donor sperm recipients undergoing treatment with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Cross-sectional study. United States donor sperm banks, US census, and fertility clinics reporting to Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS). Sperm donors from 18 banks, men aged 18-39 years based on the 2021 Census Current Population Survey (CPS), and recipients of donor sperm for IVF/ICSI in clinics reporting to SART CORS from January 1, 2018 to December 31, 2020. Race/Ethnicity MAIN OUTCOME MEASURE: Proportions of sperm donors and donor sperm recipients undergoing IVF/ICSI identifying as each racial and ethnic group. Eighteen donor sperm banks were identified, encompassing 1,503 donors. Of these donors, 60.9% identified as White compared with 55.1% of the US male population, p<0.001 and 67.7% of donor sperm recipients, p<0.001. Proportions of donors identifying as Asian or two or more races were larger than those of US men and donor sperm recipients (Asian: 18.6% vs. 6.5%, p<0.001 and 18.6% vs. 10.2%, p<0.001; two or more races: 11.6% vs. 2.2%, p<0.001 and 11.6% vs. 1.7%, p<0.001). In contrast, Black donors were underrepresented when compared to the US population of men and donor sperm recipients (2.8% vs. 12.9%, p<0.001 and 2.8% vs. 13.0%, p<0.001). Hispanic donors were underrepresented when compared to the US population of men (6.0% vs. 22.2%, p<0.001). Percentages of Hispanic sperm donors and donor sperm recipients were similar (6.0% vs. 7.0%, p=0.17). The racial and ethnic distribution of sperm donors differs significantly from the demographics of the US male population and US donor sperm recipients undergoing IVF/ICSI. These findings suggest a need for targeted recruitment efforts of Black sperm donors.

Gestational carrier cycles: embryology trends, national guideline compliance, and resultant perinatal outcomes in the United States, 2014–2020

The increased use of gestational carriers has expanded family-building opportunities for people and couples unable to carry pregnancies on their own. National American Society of Reproductive Medicine guidelines for gestational carriers have changed over time to reflect advances in reproductive technology and mounting evidence supporting the medical benefits associated with singleton gestations. Assess changes in gestational carrier cycle practice patterns and resultant pregnancy outcomes in the United States in relation to changing national American Society of Reproductive Medicine guidelines, which changed in 2013 and2017. This retrospective study used data from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System and included all cycles that were reported from 2014-2020 involving an embryo transfer to a gestational carrier. Binomial regression models evaluated trends in preimplantation genetic testing for aneuploidy, American Society of Reproductive Medicine guideline adherence, number of embryos transferred, and pregnancy outcomes over time. Of the 40,177 gestational carrier transfer cycles from 2014-2020, there was a significant increase in frozen-thawed cycles (41.3% increase), use of assisted hatching (53.4% increase), intracytoplasmic sperm injection (50.0% increase), and preimplantation genetic testing for aneuploidy (155.7% increase). The likelihood of preimplantation genetic testing for aneuploidy was higher in 2020 than in 2014 for autologous oocyte transfers to gestational carriers, both for those aged ≥38 years (adjusted relative risk, 2.38 [95% confidence interval, 2.11-2.70]) and than those aged <38 years (adjusted relative risk, 2.85 [95% confidence interval, 2.58-3.15]). As preimplantation genetic testing for aneuploidy usage increased, single embryo transfer rose for both autologous (adjusted relative risk, 2.22 [95% confidence interval, 1.94-2.50]) and donor cycles (relative risk, 1.91 [95% confidence interval, 1.81-2.02]). This shift toward single embryo transfer corresponded with a decrease in multiple embryo transfer by 79.2% and subsequent decreases in multiple gestations by 68.8% in donor and 73.6% in autologous oocyte cycles from 2014-2020. Gestational carrier cycles remained highly adherent to changing American Society of Reproductive Medicine guidelines throughout the study period. Among live births, there was a 19.4% and 7.9% increase in term deliveries among donor and autologous oocyte cycles, respectively, from 2014 to2020. Practice patterns have drastically changed throughout the study period, with major increases in the use of preimplantation genetic testing for aneuploidy, intracytoplasmic sperm injection, assisted hatching, and frozen transfers. In response to changing American Society of Reproductive Medicine guidelines, the use of multiple embryo transfers has decreased for gestational carrier cycles with subsequent decreases in multiple gestations and miscarriages and slight increases in live birth rates.

Psychosocial outcomes of children born via embryo donation.

What are parents' perceptions of their relationships with and the psychosocial adjustments of their children who are born via embryo donation? Families created through embryo donation have well-adjusted parent-child relationships and reassuring child psychosocial outcomes. Embryo donation is an effective and growing form of third-party reproduction, but there is limited research in this field. Prior studies suggest that families created through gamete donation function well regarding parent-child relationship quality and child behavioral and socioemotional adjustment. This is a cross-sectional survey study with 187 total participants. Parents of children born via embryo donation were recruited nationally by contacting all embryo donation programs registered with the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) as well as medically directed embryo donation or 'embryo adoption' centers. Participants completed three online Qualtrics questionnaires. The first was a survey including 33 questions on demographics, the procurement process, and self-reported obstetric outcomes. Participants also completed two standardized measures assessing children's behavior and parents' adjustment to parenthood: the Strengths and Difficulties Questionnaire (SDQ) and the Parental Acceptance-Rejection Questionnaire (PARQ). Scoring of the SDQ and PARQ was totaled and compared to standardized values (SDQ) or previously published results on other forms of gamete donation (PARQ), such as oocyte donation and sperm donation. On the SDQ (n = 46), the average total difficulties scores by age were: 8.2 ± 0.98 for ages 2-4, 7.6 ± 0.93 for ages 5-10, and 3.5 ± 0.77 for ages 11-17; this is compared to the normal reported range of 0-13, which indicates that clinically significant psychosocial problems are unlikely. Across all ages and individual categories (emotional symptoms, conduct problem, hyperactivity, peer problem, prosocial), scores on the SDQ were within the normal ranges. The average PARQ score (n = 70) for all respondents was 27.5 ± 1.18 (range: 24-96), suggesting perceived parental acceptance. Because this study was cross-sectional, it could not capture familial relationships over time. This survey-based study design allows for potential selection bias (parents of well-adjusted children may be more likely to participate). Additionally, the overall sample size is relatively small; however, it remains one of the largest published to date. Another significant limitation to this study is the lack of generalizability: most participants were recruited from private, faith-based, embryo donation programs who are demographically similar. Though embryo donation is an established form of third-party reproduction, it is significantly less robustly studied compared to other forms of gamete donation (oocyte or sperm donation). This study provides a larger data set with a more expanded age range of children compared to the limited number of previously published studies. Furthermore, these findings indicate a high parental disclosure rate with respect to the use of embryo donation which contrasts previous findings. No external funding source was utilized for the completion of this study. No conflicts are disclosed. N/A.

Similar pregnancy outcomes from fresh and frozen donor oocytes transferred to gestational carriers: a SART database analysis isolating the effects of oocyte vitrification.

This work aimed to study clinical and neonatal outcomes of embryos derived from frozen compared to fresh donor oocytes in gestational carrier cycles. This is a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database between 2014 and 2015, comprising of 1284 fresh transfer cycles to gestational carrier recipients of embryos resulting from fresh (n = 1119) and vitrified/thawed (n = 165) donor oocytes. Models were adjusted for gestational carrier age, preimplantation genetic testing (PGT-A), number of embryos transferred, multiple gestation, and fetal heart reduction. As our models were part of a larger analysis, intended parent BMI, smoking status, and parity were also adjusted for, but did not influence outcomes in this analysis. There was no significant difference in probability of live birth rates when comparing embryos derived from fresh and frozen donor oocytes in gestational carrier cycles. There were also no significant differences in biochemical pregnancy losses or clinical miscarriage. There were no significant differences noted in low birthweight or high birthweight infants derived from fresh versus frozen donor oocyte after transfer into a gestational carrier. The analysis of fresh and frozen donor oocytes in gestational carrier cycles provides the opportunity to assess for a possible effect of vitrification on the oocyte by controlling for differences in the uterine environment. We observed no significant differences in live birth, pregnancy loss, low birthweight or high birthweight infants when comparing fresh and frozen donor oocytes in gestational carrier cycles.

International gestational surrogacy in the United States, 2014–2020

To describe characteristics, trends, and outcomes of international gestational surrogacy cycles in the United States (US). Retrospective cohort study. All assisted reproductive technology cycles in the US reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting Systems that included an embryo transfer to a gestational carrier from 2014 to2020. International vs. US intended parents. Cycle characteristics, geographic distributions, and obstetrical outcomes. Of 40,177 embryo transfers to a gestational carrier from 2014 to 2020, 32% were for international intended parents. The number and percent of international intended parents' gestational carrier cycles increased each year from 2014 (n = 2758, 22.0%) to 2019 (n = 4905, 39.8%) with a decrease in 2020 (n = 4713, 31.8%). Compared with cycles for US intended parents, there was a larger decrease in gestational carrier cycles between 2019 and 2020 for international intended parents (3.9% vs. 32.2%). International intended parents were more likely to be male sex (41.3% vs. 19.6%), older than 42 years (33.9% vs. 26.2%) and identify as Asian race (65.6% vs. 16.5%). International intended parents were largely from China (41.7%), followed by France (9.2%) and Spain (8.5%). Gestational carriers for international intended parents were more commonly younger than 30 years (42.8% vs. 29.1%) and identified as Hispanic race (28.6% vs. 11.7%) compared with gestational carriers for US intended parents. Cycles with international intended parents were more likely to use donor eggs (67.1% vs. 43.5%), intracytoplasmic sperm injection (72.8% vs. 55.4%), and preimplantation genetic testing (79.0% vs. 55.8%). Cycles with international and US intended parents had similar obstetrical outcomes, including live birth (adjusted risk ratio 1.01, 95% confidence interval 1.00-1.03) and multiple pregnancy (adjusted risk ratio 1.00, 95% confidence interval 0.94-1.06) rates. An increasing number of international intended parents are utilizing gestational surrogacy in the US and more frequently using cost-enhancing specialized treatment techniques. This increase is potentially because of restrictive international commercial surrogacy laws and the increased availability of reproductive medical expertise. Given this growing demographic, continued examination of the volume of cross-border reproductive treatment, as well as the legal and ethical considerations, is warranted.

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

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. Retrospective cohort study of cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. All autologous and donor recipient PGT-A-tested cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System from 2014 to2017. Body mass index. 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. 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. 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.

Frozen autologous and donor oocytes are associated with differences in clinical and neonatal outcomes compared with fresh oocytes: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System Analysis

Frozen autologous and donor oocytes are associated with differences in clinical and neonatal outcomes compared with fresh oocytes: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System Analysis

Obstetric and Neonatal Outcomes After Transferring More Than One Embryo in Patients With Preimplantation Genetic Testing.

To compare obstetric and neonatal outcomes after single embryo transfer (SET) compared with multiple embryo transfer (MET) from frozen-thawed transfer cycles of embryos that underwent preimplantation genetic testing for aneuploidies (PGT-A). We conducted a retrospective cohort study from the SART CORS (Society for Assisted Reproductive Technology Clinic Outcome Reporting System) national database. Clinical and demographic data were obtained from the SART CORS database for all autologous and donor egg frozen-thawed transfer cycles of embryos that underwent PGT-A between 2014 and 2016, after excluding cycles that used frozen oocytes, fresh embryo transfer, and transfers of embryos from more than one stimulation cycle. Multivariable linear and log-binomial regression models were used to estimate the relative and absolute difference in live-birth rate, multiple pregnancy rate, gestational age at delivery, and birth weight between SET compared with MET. In total, 15,638 autologous egg transfer cycles and 944 donor egg transfer cycles were analyzed. Although the live-birth rate was higher with MET compared with SET in the autologous oocyte cycles (64.7% vs 53.2%, relative risk [RR] 1.24, 95% CI, 1.20-1.28), the multiple pregnancy rate was markedly greater (46.2% vs 1.4%, RR 32.56, 95% CI, 26.55-39.92). Donor oocyte cycles showed similar trends with an increased live-birth rate (62.0% vs 49.7%, RR 1.26, 95% CI, 1.11-1.46) and multiple pregnancy rate (54.0% vs 0.8%) seen with MET compared with SET. Preterm delivery rates and rates of low birth weight were significantly higher in MET compared with SET in both autologous and donor oocyte cycles and were also higher in the subanalysis of singleton deliveries that resulted from MET compared with SET. Despite some improvement in live-birth rate, nearly half of the pregnancies that resulted from MET of embryos that underwent PGT-A were multiples. Compared with SET, MET is associated with significantly higher rates of neonatal morbidity, including preterm delivery and low birth weight. The transfer of more than one embryo that underwent PGT-A should continue to be strongly discouraged, and patients should be counseled on the significant potential for adverse outcomes.

Comparing reproductive outcomes between conventional in vitro fertilization and nonindicated intracytoplasmic sperm injection in autologous embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System Study

ObjectiveTo compare clinical outcomes between non-indicated ICSI and conventional insemination. DesignAutologous cycles performed at SART member clinics from 2014-2017 were identified, excluding frozen oocyte cycles. Outcomes conventional insemination (IVF) or non-indicated ICSI were analyzed separately for fresh, frozen-thawed pre-implantation genetic testing (PGT) and frozen-thawed non-PGT cycles. Subjects187,520 patients underwent 318,930 cycles, 57,516 (18.0%) using conventional IVF and 261,414 ICSI (82.0%). ExposureICSI, with or without indications [male factor, prior fertilization failure or any PGT (2012 recommendations)/single-gene PGT (2020 recommendations)]. Main Outcome MeasuresOdds ratios (ORs) for live birth rates and clinical pregnancy rates were calculated after multivariable adjustment for maternal age, BMI, infertility etiologies, prior IVF births and number oocytes retrieved. ResultsICSI was indicated in 151,627 (58.0%) of cycles according to 2012 ASRM Practice Committee recommendations, and 108,895 (41.7%) according to 2020 recommendations.In multivariable models, non-indicated ICSI among fresh cycles was associated with reduced odds of completing a blastocyst-stage transfer (OR 0.72, 95% CI (0.7, 0.75), p<0.001), resulting in reduced odds of live birth (OR 0.80, 95% CI (0.78,0.83), p<0.001). Among completed fresh transfers, clinical pregnancy and live birth rates were comparable between non-indicated ICSI and IVF.Non-indicated ICSI in frozen-thawed cycles with PGT and without PGT was associated with comparable live birth and clinical pregnancy rates to IVF in multivariable models. ConclusionNon-indicated ICSI was associated with reduced blastocyst availability in fresh cycles compared with IVF, leading to lower live birth rates. Outcomes from completed transfers were clinically comparable.

Cumulative live birth rates with autologous oocytes plateau with fewer number of cycles for each year of age > 42

ObjectiveTo disaggregate the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) age category of “ > 42” and compare age-stratified cumulative live birth rates (CLBR) > 42 years old.DesignRetrospective cohort study of autologous linked ART cycles.SettingUnited States (US) National ART Database.Patient(s)Women > 42 years old without a history of prior ART cycles who underwent ART between 2014–2020 as reported to the SART CORS database.Intervention(s)Disaggregate the SART CORS age category of “ > 42” into age-stratified cumulative live birth rates (CLBR).Main Outcome Measure(s)Age-stratified cumulative live birth rates (CLBR) for women ≥ 43 years old.ResultsBetween 2014–2020, 24,650 women > 42 years old without history of prior ART underwent 58,132 cycles, resulting in 1,982 live births. Women ages 43, 44, 45, 46, 47, 48, 49, ≥ 50 achieved maximal CLBR of 9.7%, 8.6%, 5.0%, 3.6%, 2.5%, 1.5%, 2.7%, 1.3%, respectively. CLBR for women between 43–45 were significantly higher compared to those 46 and older (p < 0.05). Among women 46 and older, CLBR were not significantly different. Women ages 43 and 44 did not exhibit a significant increase in CLBR beyond the 5th cycle. Age 45 and 46 reached CLBR plateau by the 3rd cycle. Age ≥ 47 CLBR plateaued after the first cycle. After adjusting for age, race/ethnicity, BMI, nulliparity, etiology of infertility, number of oocytes retrieved, embryos transferred, blastocyst transfer, use of ICSI, PGT, and ART treatment cycle number, there was no association between markers of ovarian reserve (day 3 FSH and random AMH levels) and live birth for women > 42.ConclusionsWhile CLBR of autologous cycles from women 42 or younger generally plateau by cycle number 5, age-stratified cycles from women > 42 plateau after fewer cycles to maximize CLBR. Patient and physician expectations for maximum CLBR beyond 42 may be practically based on fewer planned cycles before reaching an age-specific CLBR plateau than may have been previously expected.

Assisted reproductive technology use and outcomes in childhood cancer survivors.

Treatment exposures for childhood cancer reduce ovarian reserve. However, the success of assisted reproductive technology (ART) among female survivors is not well established. Five-year survivors of childhood cancer in the Childhood Cancer Survivor Study were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, which captures national ART outcomes. The authors assessed the live birth rate, the relative risk (RR) with 95% confidence intervals (95% CIs), and associations with treatment exposure using generalized estimating equations to account for multiple ovarian stimulations per individual. Siblings from a random sample of survivors were recruited to serve as a comparison group. Among 9885 female survivors, 137 (1.4%; median age at diagnosis, 10years [range, 0-20 years]; median years of follow-up after age 18 years, 11years [range, 2-11 years]) underwent 224 ovarian stimulations using autologous or donor eggs and/or gestational carriers (157 autologous ovarian stimulation cycles, 67 donor ovarian stimulation cycles). In siblings, 33 (1.4%) underwent 51 autologous or donor ovarian stimulations. Of those who used embryos from autologous eggs without using gestational carriers, 97 survivors underwent 155 stimulations, resulting in 49 live births, for a 31.6% chance of live birth per ovarian stimulation (vs. 38.3% for siblings; p=.39) and a 43.9% chance of live birth per transfer (vs. 50.0%; p=.33). Prior treatment with cranial radiation therapy (RR, 0.44; 95% CI, 0.20-0.97) and pelvic radiation therapy (RR, 0.33; 95% CI, 0.15-0.73) resulted in a reduced chance of live birth compared with siblings. The likelihood of live birth after ART treatment in survivors was not affected by alkylator exposure (cyclophosphamide-equivalent dose, ≥8000mg/m2 vs. none; RR, 1.04; 95% CI, 0.52-2.05). Childhood cancer survivors are as likely to undergo treatment using ART as sibling controls. The success of ART treatment was not reduced after alkylator exposure. The results from the current study provide needed guidance on the use of ART in this population.

O-050 The impact of embryo biopsy on obstetric and neonatal outcomes

Abstract Background Preimplantation genetic testing of embryos (PGT) was performed first in 1990 to prevent the transmission of X-linked disease. Since then, the technique has improved to include couples who are both carriers of the same autosomal recessive disorder, to those with balanced translocations having recurrent pregnancy loss, and to women with advanced maternal age who are at higher risk for having aneuploid embryos. Originally, PGT involved biopsy of the polar body or of one blastomere of a cleavage stage embryo for diagnosis. The contemporary practice of PGT involves the culture of embryos to the blastocyst stage (5-7 days after fertilization), with biopsy of several trophectoderm cells that would become the placenta, transport of biopsy tissue off-site for genetic analysis, and cryopreservation of blastocysts until biopsy results are available. A single euploid embryo is then transferred into the uterus as a frozen embryo transfer. Objective We sought to determine if removal of these cells for preimplantation genetic testing was associated with adverse obstetrical or neonatal outcomes after frozen-thawed single embryo transfer compared to frozen-thawed single embryo transfer without biopsy. Further, we review other studies of contemporary practice of PGT to draw conclusions about the safety of the practice. Study design We linked assisted reproductive technology surveillance data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System to birth certificates and maternal and neonatal hospitalization discharge diagnoses in Massachusetts, USA, from 2014-2017, considering singleton births after frozen-thawed single embryo transfer. We compared outcomes of cycles having embryo biopsy (n = 585) to those having no biopsy (n = 2,191), adjusting for mother’s age, race, education, parity, body mass index, birth year, insurance, and all infertility diagnoses (Sites CK et al, Am J Obstet Gynecol 2021;225:285.e1-7). Results With no biopsy used as the reference, we found no differences between no biopsy and biopsy groups with respect to preeclampsia, pregnancy-induced hypertension, placental disorders (placental abruption, placenta previa, placenta accreta, placenta increta, and placenta percreta), preterm birth, low birthweight, cesarean delivery, gestational diabetes mellitus, or maternal or infant length of stay after delivery. Comparing our outcomes to 4 other studies of contemporary PGT practice of frozen-thawed embryo transfers (Zhang WY Fertil Steril 2019, Li M Am J Obstet Gynecol 2020, Makhijani R Hum Reprod 2021, He H Fertil Steril 2019), our data are consistent with no effect of biopsy on low birth weight, pregnancy-induced hypertension, gestational diabetes, placenta previa, and placenta accreta. A slight decrease in preterm delivery (RR 1.10, CI 1.02-1.18), slight reduction in cesarean section (RR 0.90, CI 0.82-0.99), and increase in intrauterine growth restriction (RR 1.21, CI 1.06-1.38) are reported with biopsy in a systematic review (Hou W, Fertil Steril 2021). The increase in risk for intrauterine growth restriction with biopsy was influenced by one study (Li M Am J Obstet Gynecol 2020). Conclusion Embryo biopsy of trophectoderm cells for PGT in contemporary practice appears to be safe generally with respect to maternal and neonatal outcomes. There is no clear increase in diagnoses related to placentation (preeclampsia, pregnancy-induced hypertension, placental disorders, preterm birth, low birthweight), cesarean delivery, gestational diabetes mellitus, or maternal or infant length of stay after delivery. Further study of a possible increase in intrauterine growth restriction with biopsy is indicated.

O-111 Conventional stimulation remains the gold standard

Abstract Ovarian stimulation (OS) remains a crucial step of IVF process since cycle outcomes per cycle after OS are remarkably higher when compared to a natural or modified natural cycle. Within the concept of OS, two approaches are purposed: On one hand, “mild” stimulation claims for the use of low doses of gonadotrophins in order to yield a moderate number of eggs that should be enough to achieve a pregnancy. On the other, the so called “conventional” stimulation aims to maximize ovarian response, with the goal of obtaining the higher number of embryos that is possible and therefore increase the number of attempts per pick up to reach the highest chance of pregnancy for each patient in one cycle. Defenders of mild stimulation, claim that obtaining oocytes beyond a certain response (classically eight eggs) is useless, since these surplus oocytes won’t be able to provide good quality embryos. In other words, this statement is based in a hypothesis according to which a soft stimulation of the ovaries would lead them to mature only the good quality eggs, while those of lower quality would not respond to these low doses and would remain immature in the ovaries. A few numbers of old studies performed with outdated technologies support this this concept. However, a large body of evidence shows that the contrary is true. Old studies that related ovarian response to cycle outcome considering only the chances of achieving a live birth after just a fresh embryo transfer, showed that live birth rate increased as the ovarian response did up to around 15 oocytes, while it shows a “plateau” beyond this response. But moreover, more recent studies in which the cumulative live birth rate achieved after one live birth is achieved or until all viable embryos that were cryopreserved were transferred, shows that it improves linearly as the ovarian response does, starting to plateau only for ovarian responses larger than 35-40 eggs. A very recent study that analyses more than 400,000 cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART) confirms these figures. This large sample allows for stratified analysis according to age, BMI, AMH or infertility diagnoses that further confirm the findings. Altogether, these studies show that the concept of some kind of “oocyte quality selection” happens when a mild stimulation is used does not really happen. Large ovarian responses increase the number of good and bad quality oocytes equally. The idea of ovarian stimulation hampering oocyte quality has been around for more than 30 years. Theorical concepts based on observations in the animal model suggested that this might be the case. However, studies in humans have been unable to prove this hypothesis. In this context, the best model to prove this concept is the intra-patient comparison between the non-stimulated and the conventionally stimulated cycle. Our group has performed two studies following this approach so far. In the first one, we included 46 oocyte donors. PGT-A was performed to the embryos obtained in both cycles, which at time was performed on day 3 embryos with FISH technology. The study showed that there were no significant differences in the aneuploidy rate between the 2 cohorts of embryos (34.8% vs 32.8%), suggesting no harm of ovarian stimulation. These findings have been recently confirmed in 40 infertile patients aged 30-38, in which PGT-A was done with a comprehensive chromosomal analysis using NGS after blastocyst biopsy. In conclusion, research and clinical evidence show that conventional OS does not harm oocyte quality and increases the cumulative birth rate per oocyte pick-up, making it as the first choice for treating patients with IVF. Trial registration number XXXX

Causal inference indicates that poor responders have similar outcomes with the antagonist protocol compared with flare

To use causal inference to investigate whether the flare or antagonist protocol is better for poor responders going through controlled ovarian stimulation. A retrospective study. Retrieval cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Patients in the United States underwent autologous invitro fertilization cycles from 2014 to 2019 using either the flare or antagonist protocol. Not applicable. Primary outcomes included oocytes retrieved, fertilized oocytes (2PNs), blastocysts, the cumulative live birth rate (CLBR), and cycle cancelation rate. After propensity score matching, patients with a predicted poor response (antimüllerian hormone, <0.5) on their first invitro fertilization cycle had similar outcomes on the antagonist protocol (CLBR of 14.2%, 95% confidence intervals [CIs]: 13.6%, 14.8%) compared with flare (CLBR of 13.6%, 95% CIs: 12.4%, 14.8%). We evaluated patients undergoing a second cycle after having a poor response (<4 oocytes retrieved) on their first cycle. Patients in the antagonist-to-antagonist group had a similar change in outcomes between the first and second cycles (average CLBR improvement of 13.9%, 95% CIs: 12.1%, 15.6%) compared with the antagonist-to-flare group (average CLBR improvement of 14.4%, 95% CIs: 10.9%, 18.3%). In addition, patients in the flare-to-antagonist group had a similar change in outcomes between the first and second cycles (average CLBR improvement of 10.4%, 95% CIs: 6.6%, 14.5%) compared with the flare-to-flare group (average CLBR improvement of 9.0%, 95% CIs: 5.1%, 13.4%). Poor responders have similar outcomes on an antagonist protocol compared with a flare protocol for both the first and second cycles.

Effect of state insurance mandates on racial/ethnic disparities in the utilization and outcomes of donor oocyte–assisted reproductive technologies

To characterize racial/ethnic disparities in donor oocyte-assisted reproductive technology (ART) nationwide and examine the impact of state insurance mandates on disparities in utilization and outcomes. Retrospective cohort study. Donor oocyte ART cycles in the United States (US). Women who underwent donor oocyte ART in 2014-2016, as reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Race/ethnicity of oocyte recipients. Live birth through 1 or more donor oocyte ART cycles in 2014-2016 per recipient. We analyzed 44,033 donor ART cycles performed for 28,157 oocyte recipients, 99.2% (27,919/28,157) of whom were aged 25-54 years. Race/ethnicity data were reported for 61.4% (17,281/28,157) of the recipients. Among recipients aged 25-54 years with race data, 65.8% (11,264/17,128) identified as non-Hispanic White, whereas 58.9% were White among women aged 25-54 in the 2016 US census. In contrast, Black recipients comprised 8.3% of those aged 25-54 years with race data, compared with 13.7% nationwide. Among White recipients, 7.0% (791/11,356) lived in states with donor ART mandates (Massachusetts/New Jersey), compared with 6.5% (93/1,439) of Black recipients, 8.1% (108/1,335) of Hispanic recipients, and 5.8% (184/3,151) of Asian recipients. Black recipients had a higher median age and body mass index and were more likely to have uterine factor infertility. White recipients had the highest cumulative probability of live birth in the nonmandate (64.6%, 6,820/10,565) and mandate (69.5%, 550/791) states, followed by Asian recipients (nonmandate, 63.4% [1,881/2,967]; mandate, 65.2% [120/184]), Hispanic recipients (nonmandate, 60.5% [742/1,227]; mandate, 68.5% [74/108]), and Black recipients (nonmandate, 48.7% [655/1,346]; mandate, 48.4% [45/93]). The multivariable Poisson regression adjusting for donor's age and recipient's age, body mass index, nulliparity, history of recurrent pregnancy loss, diminished ovarian reserve, tubal factor and uterine factor infertility, prior ART treatment, use of preimplantation genetic testing, cumulative number of embryos transferred, use of blastocysts, and frozen-thawed transfers, demonstrated that Black recipients had a lower cumulative probability of a live birth than White recipients (relative risk [RR], 0.82; 95% confidence interval [CI], 0.77-0.87), as were Hispanic recipients (RR, 0.93; 95% CI, 0.89-0.99) and Asian recipients (RR, 0.96; 95% CI, 0.93-0.99). These disparities were not modified by state mandate for donor ART. State mandates for donor oocyte ART in their current forms are insufficient in decreasing racial/ethnic disparities.

The Risks of Birth Defects and Childhood Cancer With Conception by Assisted Reproductive Technology

ABSTRACT As the proportion of births conceived with assisted reproductive technology (ART) continues to increase, a growing body of literature continues to examine the risks involved such as the higher risk of birth defects. Recently, several studies have suggested that ART-conceived children may have a greater risk of childhood cancer. This population-based cohort study aimed to evaluate the risk of childhood cancer as a function of birth defect status and method of conception. Data were obtained from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, birth certificates (2004–2013), birth defect registries, and cancer registries in 4 states. The Society for Assisted Reproductive Technology Clinic Outcome Reporting System contains comprehensive information on ART procedures from 86% of all clinics and more than 92% of all ART cycles in the United States. Assisted reproductive technology cycles reported from January 2004 to December 2017 that resulted in live births were included in this study. For each ART-conceived delivery, the subsequent 10 deliveries were selected as the non-ART comparison group, and siblings of each ART birth were selected as the ART sibling group. The ART group was divided into 4 subgroups based on the combination of oocyte source (autologous or donor) and embryo state (fresh or thawed). A host of independent variables with established associations on birth defects, cancer, and/or ART were selected a priori for inclusion in statistical models. The total study population included 165,125 ART-conceived children, 31,524 non-ART siblings, 12,451 children born as a result of infertility treatment without ART (ovulation induction/intrauterine insemination [OI/IUI]), and 1,353,440 naturally conceived children. A total of 29,571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect. Compared with naturally conceived children, risks for defects were increased for all other groups for nonchromosomal (adjusted odds ratios [AORs] ranged from 1.20 to 1.24, except for donor-fresh), blastogenesis (AORs, 1.22–1.74), cardiovascular (AORs, 1.04–1.26), gastrointestinal (AORs, 1.28–2.01), musculoskeletal (AORs, 1.10–1.48), and genitourinary among male children (AORs, 1.15–1.40, except for donor-fresh). Orofacial defects were increased in the OI/IUI and autologous-fresh and autologous-thawed groups (AORs, 1.26–1.42). The risk of any cancer was increased among ART autologous-fresh and non-ART siblings (hazard ratios [HRs], 1.31 and 1.34, respectively). A total of 127 children had both birth defects and cancer, with 53 (42%) of these children having leukemia. A Cox proportional hazards regression model identified 2 components for the risk of cancer: method of conception and type and number of birth defects. The presence of chromosomal defects was strongly associated with cancer risk (HRs, 8.70 for all cancers and 21.90 for leukemia), and this was further increased in the presence of both chromosomal and nonchromosomal defects (HRs, 21.29 for all cancers, 64.83 for leukemia, and 4.71 for embryonal tumors). The results of this study demonstrate that compared with naturally conceived children a significantly increased risk of nonchromosomal birth defects was found among children conceived with infertility treatment and that the risk of cancer was increased by greater than 30% among non-ART siblings and ART children born from autologous-fresh cycles. Among both naturally conceived and ART-conceived children, the presence of birth defects was associated with a greater risk of cancer.

Polycystic Ovary Syndrome and Risk of Adverse Pregnancy Outcomes: A Registry Linkage Study From Massachusetts

ABSTRACT Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women, affecting approximately 6% to 15% of reproductive-aged women. Polycystic ovarian syndrome is associated with obesity, metabolic syndrome, impaired glucose tolerance, insulin resistance, adverse pregnancy outcomes, and infertility. Previous meta-analyses and reviews have suggested that women with PCOS are at an increased risk of pregnancy complications, although many of the studies included are small and may not be generalizable. This population-based study aimed to investigate whether women with a previous history of PCOS had greater risk of adverse maternal and pregnancy outcomes compared with women without a diagnosis of PCOS accounting for potential confounding factors. Data were obtained from 3 sources: the Massachusetts Pregnancy to Early Life Longitudinal Data System, the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, and the Massachusetts All-Payers Claims Database. Maternal outcomes investigated included gestational diabetes, hypertensive disorders of pregnancy, cesarean delivery, and placental abnormalities. Neonatal outcomes investigated were size for gestational age, low birth weight, prematurity, prolonged delivery, and hospital stay. Infant conditions and diagnoses during the first year of life were also investigated. Deliveries were classified into groups of noninfertile, subfertile/infertile, or assisted reproductive technology. The relative risks (RRs) and 95% confidence intervals (CIs) of adverse outcomes were estimated with a log-link and Poisson distribution, and multivariable models were a priori adjusted for potential confounding factors. A total of 3552 deliveries to women with a history of PCOS and 88,273 deliveries to women without a diagnosis of PCOS were included. When adjusting for maternal age, prepregnancy body mass index (BMI), education, race/ethnicity, plurality, birth year, and history of hypertension and diabetes, women with a history of PCOS had a 51% greater risk of gestational diabetes (RR, 1.51; 95% CI, 1.38–1.65). Women with a history of PCOS were also at a greater risk of pregnancy-induced hypertension, preeclampsia, and eclampsia (RR, 1.25; 95% CI, 1.15–1.35) and higher risk of cesarean delivery (RR, 1.07; 95% CI, 1.02–1.11). Women with a history of PCOS were more likely to deliver prematurely (RR, 1.17; 95% CI, 1.06–1.29), and infants born to mothers with a history of PCOS were more likely to have a prolonged neonatal hospital stay (RR, 1.23; 95% CI, 1.01–1.19). Among women with a BMI &lt;30 kg/m2, PCOS was associated with a greater risk of gestational diabetes (RR, 1.60; 95% CI, 1.42–1.80) than among those with a BMI &gt;30 kg/m2 (gestational diabetes: RR, 1.37; 95% CI, 1.21–1.57). The results of this study demonstrate that women with a history of PCOS were more likely to experience gestational diabetes, hypertensive disorders of pregnancy, and cesarean delivery, and their neonates were more likely to be born premature and have a prolonged neonatal hospital stay.