Reproductive Technology Clinic Outcome Reporting Research Articles

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 A few numbers of old studies performed with outdated technologies support this this concept.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.

Effects of parity on preterm delivery in twin gestations conceived with in vitro fertilization

To determine the relationship between prior obstetrical history and gestational age at delivery in a twin pregnancy. Retrospective cohort study using theUnited States Society for Assisted Reproductive Technology Clinic Outcomes Reporting System database. Clinic-based data. Patients undergoing invitro fertilization (IVF) in the United States with live delivery of twins. None. The main outcome measures are median gestational age at delivery and rate of preterm delivery (before 37 weeks). The median gestational age at delivery of IVF-conceived twins was 36.3 (interquartile rate 34.4, 37.6) weeks for nulliparous women, 35.9 (34.0, 37.1) weeks for parous women with a prior preterm birth, and 36.7 (35.1, 37.7) weeks for parous women without a prior preterm birth. The rate of preterm delivery was 61% for nulliparous women, 70% for parous women with a prior preterm birth, and 55% for parous women without a prior preterm birth. Parous women without a history of preterm delivery had lower rates of preterm delivery in a subsequent twin pregnancy than nulliparous women. Nulliparous women had lower rates of preterm delivery compared with parous women with a history of preterm delivery.

A higher number of oocytes retrieved is associated with an increase in fertilized oocytes, blastocysts, and cumulative live birth rates

To investigate the association between the number of oocytes retrieved and the numbers of fertilized oocytes and blastocysts and cumulative and primary transfer live birth rates (LBRs). Retrospective study. Retrieval cycles and linked embryo transfers from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Patients in the United States undergoing autologous invitro fertilization cycles from 2014 to 2019 (n = 402,411 cycles). None. Normally fertilized oocytes, blastocysts, and cumulative and primary transfer LBRs. There was a strong positive linear correlation between oocytes and fertilized oocytes and between oocytes and blastocysts. The cumulative LBR increased rapidly with the number of oocytes retrieved to approximately 16-20 oocytes, at which point it continued to increase but with diminishing returns. The increasing trend of the cumulative LBR was observed when stratifying patients by age and antimüllerian hormone and after controlling for confounding variables using multivariate logistic regression. The primary transfer LBR also increased with the number of oocytes to approximately 16-20 oocytes, at which point it plateaued but did not decline. A higher number of oocytes retrieved improves the cumulative LBR without impairing the primary transfer LBR. Thissuggests that ovarian stimulation strategies should aim to safely maximize the number of oocytes retrieved.

Development of a Model to Estimate the Optimal Number of Oocytes to Attempt to Fertilize During Assisted Reproductive Technology Treatment

Surplus cryopreserved embryos pose a challenge for in vitro fertilization patients and clinics; with Roe v. Wade overturned, some states may deem the discarding of surplus embryos illegal, radically changing in vitro fertilization practice. An evidence-based tool would help limit surplus embryo creation. To develop a prediction tool for determining how many oocytes should be exposed to sperm to create embryos to conserve the chance of live birth while minimizing surplus embryos. This diagnostic study used data from member clinics of the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System between 2014 to 2019. A total of 410 719 oocyte retrievals and 460 577 embryo transfer cycles from 311 237 patients aged 18 to 45 years old who initiated their first oocyte stimulation cycle between January 1, 2014, and December 31, 2019, were included. Data were analyzed from February to June 2022. Female patient age, anti-mullerian hormone level, diminished ovarian reserve diagnosis, number of oocytes retrieved, and the state where the clinic is located were included in the final models. The algorithm was based on 3 models with outcomes: (1) day of transfer; (2) proportion of retrieved oocytes that become usable blastocysts; and (3) number of blastocysts needed for transfer for 1 live birth to occur. The median (IQR) age at stimulation cycle start was 35 (29-32) years and the median (IQR) number of oocytes retrieved was 10 (6-17). The likelihood of recommending that all oocytes be exposed to sperm increased with age; less than 20.0% of retrievals among patients younger than 32 years and more than 99.0% of retrievals among patients older than 42 years received recommendations that all oocytes be exposed to sperm. Among cycles recommended to expose fewer than all oocytes, the median (IQR) numbers recommended for 1 live birth were 7 oocytes (7-8) for patients aged less than 32 years, 8 (7-8) for patients aged 32 to 34 years, and 9 (9-11) for patients aged 35 to 37 years. In this diagnostic study of in vitro fertilization cycles, a prediction tool was developed to aid clinicians in determining the optimal number of oocytes to expose to sperm, reducing the number of unused embryos created and immediately addressing current patient and clinician concerns.

The effect of trophectoderm biopsy for preimplantation genetic testing on fetal birth weight and preterm delivery.

Preimplantation genetic testing for aneuploidy (PGT-A) is used as part of in-vitro-fertilization (IVF) to assist in selection of euploid embryos, which involves performing trophectoderm biopsy. The effect of possible trauma caused by biopsy and the implication on pregnancy is unknown. Hence, the objective of the study was to determine if embryo biopsy for PGT-A affects birth weight or preterm birth rate. Using National Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data, we identified 6352 cycles which had single embryo transfer (SET) and a singleton live birth following frozen embryo transfer (FET) between 2014 and 2015. From the initial cohort of 25,121 fresh stimulation cycles, 6352 cycles were included who had a singleton live birth following FET. A total of 3482 (54.8%) had PGT-A confirmed euploid embryos and 2870 (45.2%) had embryos selected based on morphology for transfer. No difference in birthweight (g) was noted when FET was performed using PGT-A confirmed euploid embryos as compared to non-tested morphologically selected embryos (3370.7 vs. 3354.5, adjusted regression coefficient 11.4; 95% CI: -12.6; 35.3). As compared to morphologically selected embryos, performance of PGT-A did not increase the risk of small for gestation age (SGA) (3.9% vs. 4.1%, OR: 1.13; 95% CI: 0.86-1.50), low birth weight (LBW) (<2500 g but ≥1500 g) (5.8% vs. 5.5%, OR: 0.90; 95% CI: 0.66-1.21), or very low birthweight (<1500 g) (1.3% vs. 1.0%, OR: 0.44; 95% CI: 0.44 (0.18-1.10). There was no increased risk of preterm birth (PTB) associated with pregnancy resulting from PGT-A embryos vs. non PGT-A embryos (15.8% vs. 16.4%, OR: 0.94; 95% CI: 0.81-1.09). In our study, trophectoderm biopsy for PGT-A did not increase the risk of SGA, LBW or PTB in IVF pregnancies.

Body mass index is negatively associated with a good perinatal outcome after in vitro fertilization among patients with polycystic ovary syndrome: a national study

To evaluate the association between body mass index (BMI) and good perinatal outcomes after invitro fertilization (IVF) among women with polycystic ovary syndrome (PCOS). Retrospective cohort study using 2012-2015 Society for Assisted Reproductive Technology Clinic Outcomes Reporting System data. Fertility clinics. To identify patients most likely to have PCOS, we included women with a diagnosis of ovulation disorder and serum antimüllerian hormone >4.45 ng/mL. Exclusion criteria included age ≥ 41 years, secondary diagnosis of diminished ovarian reserve, preimplantation genetic testing, and missing BMI or primary outcome data. None. Good perinatal outcome, defined as a singleton live birth at ≥ 37 weeks with birth weight ≥ 2,500 g and ≤ 4,000 g. The analysis included 9,521 fresh, autologous IVF cycles from 8,351 women. Among women with PCOS, the proportion of cycles with a good perinatal outcome was inversely associated with BMI: underweight 25.1%, normal weight 22.7%, overweight 18.9%, class I 18.4%, class II 14.9%, and class III or super obesity 12.2%. After adjusting for confounders, women in the highest BMI category had 51% reduced odds of a good perinatal outcome compared with normal weight women (adjusted odds ratio 0.49, 95% confidence interval 0.36-0.67). Among women with PCOS undergoing fresh, autologous IVF, the odds of a good perinatal outcome decline with increasing BMI. Women with PCOS should be counseled that the odds of achieving a good perinatal outcome decrease as their weight increases.

Anti-Müllerian Hormone and Follicle-Stimulating Hormone Are Poor Independent Predictors of Live Birth After Assisted Reproductive Technology.

To query if anti-Müllerian hormone (AMH) and/or follicle-stimulating hormone (FSH) predict live birth at the University of Colorado Advanced Reproductive Medicine (CU ARM). This was a retrospective analysis using the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System database at CU ARM from 2017 to 2019 to identify the pregnancy outcomes of the initial fresh or frozen embryo transfer (FET) and their corresponding AMH and FSH. Fisher's exact tests were used to identify differences in pregnancy outcome by age group, and area under the receiver operator characteristic curves was used to quantify live birth prediction. A total of 1083 records from 557 patients were reviewed. After only including the first autologous transfer, 270 cycles were analyzed. Overall live birth (L/B) rate was 58.15% (157/270), which declined with increasing age group (p ≤ 0.01). Although AMH significantly decreased with increasing age (p < 0.001), it was not associated with pregnancy outcome (3.54ng/mL vs. 3.41ng/mL, p = 0.56); this relationship was unchanged after controlling for age in logistic regression models (p = 0.52). FSH was also not significantly related to pregnancy outcome (7.00IU/L vs 6.00IU/L, p = 0.15), and this relationship did not change after controlling for age (p = 0.61). Using AUC, the only variable predictive of live birth was age (p = 0.002). AMH and FSH are not associated with the probability of live birth. Only age was significantly associated with live birth in this series. AMH and FSH should therefore be used cautiously when counseling patients about ART outcomes.

A unique placenta previa risk factor profile for pregnancies conceived with assisted reproductive technology

To define specific risk factors for placenta previa in pregnancies conceived with assisted reproductive technology (ART). Retrospective cohort. Fertility centers and inpatient obstetric units in Massachusetts. Patients conceiving with ART and delivering at 20 weeks gestation or later between 2011 and 2017 in Massachusetts. Patient demographic and medical factors and specific components of their cycles. Data were obtained by linking vital records of the State of Massachusetts to reproductive clinic data obtained from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, and then supplementing this information with laboratory and obstetric data from 2 large academic hospitals. Associations were tested between multiple cycle- and patient-related factors and placenta previa or low-lying placenta at delivery. After testing for confounders, multivariate models were adjusted for maternal age, history of prior cesarean delivery and birth plurality, and are reported as adjusted relative risks (aRR). We included 18,939 pregnancies, with 553 (2.9%) having placenta previa at delivery. Advanced maternal age (aRR, 1.25; 95% confidence interval [CI], 1.06-1.48), endometriosis, (aRR, 2.22; 95% CI, 1.71-2.86), and controlled ovarian hyperstimulation (aRR, 1.33; 95% CI, 1.12-1.59) were associated with placenta previa, whereas multiple births (aRR, 0.63; 95% CI, 0.48-0.81) and a history of polycystic ovary syndrome or ovulation disorders (aRR, 0.59; 95% CI, 0.46-0.75) had negative associations. The endometriosis association was strong in nulliparas and the controlled ovarian hyperstimulation association was strong in parous patients in a stratified analysis. No association was seen with prior history of cesarean delivery. Patients conceiving with ART do not have the typical previa risk factors of prior cesarean delivery and multiple gestations, whereas endometriosis and fresh embryo transfers contributed moderate risk. The embryo transfer process itself may affect previa development in this population.

The risks of birth defects and childhood cancer with conception by assisted reproductive technology.

The risks of birth defects and childhood cancer with conception by assisted reproductive technology.

Association between embryo morphological quality and birth weight for singletons conceived via autologous fresh embryo transfer: an analysis using Society for Assisted Reproductive Technology Clinical Outcomes Reporting System

To determine if morphologically suboptimal embryo quality is associated with adverse perinatal outcomes. A retrospective cohort. SART CORS database. Singletons conceived from autologous invitro fertilization fresh cycles. None. Birth weight (gram), birth weight z-score, low birth weight (LBW), small for gestational age (SGA), and large for gestational age (LGA). Among 5,869 invitro fertilization fresh cycles, 71.1% transferred morphologically good embryos, and 27.0% and 1.9% transferred fair and poor embryo(s), respectively. Compared with singletons conceived from good embryos, singletons from poor embryos had a higher birth weight (3,415.8 ± 562.0 vs. 3,202.7 ± 639.9). Proportions of LBW, SGA, and LGA were comparable across embryo quality groups. Multivariate regression analysis comparing perinatal outcomes from fair vs. good embryos showed no association for birth weight (0.69-gram difference; 95% CI, -24.30-25.68), birth weight z-score (Coefficient, 0.00; 95% CI, -0.07-0.08), LBW (adjusted odds ratio [aOR], 0.84; 95% CI, 0.63-1.11), SGA (aOR, 0.93; 95% CI, 0.78-1.11), and LGA (aOR, 1.07; 95% CI, 0.86-1.33). Stratified analysis, considering cleaved and blastocyst embryo transfers separately, confirmed these findings. Sensitivity analysis revealed increased odds of LGA (aOR, 1.53; 95% CI, 1.04-2.24) with fair-quality embryos only among single embryo transfer cycles. Once a singleton live birth from fresh embryo transfer is achieved, fair morphological embryo quality is not associated with a reduction in birth weight or increased risks of LBW, SGA, and LGA.

Disparities in Oncofertility: Assisted reproductive technology utilization and fertility-sparing oncology care in women with a history of breast, ovarian, cervical or endometrial cancer (094)

Disparities in Oncofertility: Assisted reproductive technology utilization and fertility-sparing oncology care in women with a history of breast, ovarian, cervical or endometrial cancer (094)

Association between duration of controlled ovarian stimulation and live birth rate in women undergoing In Vitro Fertilization: a SART CORS analysis

Background: In-Vitro Fertilization (IVF) treatment involves synchronization of multiple time-sensitive events, most of which are rate-limiting too. Controlled ovarian stimulation (COS) is one such event. The reproductive outcomes based on the duration of COS (d-COS) in a fresh, IVF embryo transfer (ET) are not well established and therefore, remains largely uncertain. Objective: To evaluate the association between d-COS and live birth rate (LBR) in women undergoing a fresh IVF-ET using autologous oocytes. Methods: A retrospective cohort study was conducted using a US nationwide IVF register – SARTCORS (Society for Assisted Reproductive Technology Clinic Outcomes Reporting System). From a total of 93,889 cycles, we included 56,666 fresh, autologous, IVF - ET treatment cycles from January 2014 through December 2015, with follow-up until October 2016. Adjusted odds and risk ratio with 95% confidence intervals were estimated while controlling for multiple demographic factors and other potential confounders. Variables and outcomes: The primary exposure variable was d-COS defined as the difference in days between gonadotrophin administration and oocyte retrieval. The primary outcome measure was live birth following a fresh IVF-ET. Secondary outcome measures included biochemical pregnancy rate, miscarriage rate, implantation rate and clinical pregnancy rate. Results: A total of 56,666 treatment cycles (mean [SD] age of 33.9 [4.47], BMI of 26.1 [6.02], AMH value of 2.19 [3.37]), and a baseline FSH value of 7.62 [3.49]) underwent a fresh IVF-ET. The LBR after a combined analysis for all ages and all protocols was 44.2 % (n = 25043). In the combined analysis, there was a statistically significant decrease in the live birth rate with LBR with d-COS beyond 10 days. The adjusted OR (95% CI) of LBR for a woman who had 11, 12, 13 and ≥14 days of COS, compared to optimal duration of 10 days was 0.97 (0.87-0.99), 0.94 (0.8-1), 0.83 (0.77-0.89) and 0.73 (0.68-0.79) respectively. The AOR (95% CI) of miscarriage rates for a woman who had 11, 12, 13 and ≥14 days of COS, compared to referent was 1.12 (1-1.26), 0.99 (0.87-1.12), 1.03 (0.90 -1.17) and 1.04 (0.90 - 1.2) respectively. With increasing d-COS, the implantation rate (IR) and clinical pregnancy rate (CPR) also showed a decreasing trend, as with other reproductive outcomes. The RR (95% CI) for implantation rate in a woman who had 11, 12, 13 and ≥14 days of COS, compared to referent was 0.97 (0.93-1), 0.97 (0.93-1.01), 0.91 (0.87-0.95) and 0.86 (0.82-0.9). The adjusted OR (95% CI) of CPR for a woman who had 11, 12, 13 and ≥14 days of COS, compared to referent was 0.95 (0.89-1.01), 0.93 (0.87-0.99), 0.8 (0.75-0.86) and 0.7 (0.65-0.75) respectively. Conclusions and Relevance: In this nationwide cohort study of women undergoing fresh IVF-ET using autologous oocytes, controlled ovarian stimulation lasting approximately 10-days was associated with an optimal live birth rate.

Impact of increasing antimüllerian hormone level on in vitro fertilization fresh transfer and live birth rate

ObjectiveThe objective of our study was to assess the association between AMH and live birth among women with elevated AMH undergoing first fresh IVF. Serum antimüllerian hormone (AMH) correlates with oocyte yield during in vitro fertilization (IVF). However, there are limited data regarding IVF outcomes in women with elevated AMH levels.DesignRetrospective cohort study using the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System database from 2012–2014.SettingFertility clinics reporting to Society for Assisted Reproductive Technology.Patient(s)First, fresh, autologous IVF cycles with elevated AMH levels (≥5.0 ng/mL). Subanalyses were performed to examine patients with or without polycystic ovary syndrome (PCOS).Intervention(s)None.Main Outcome Measure(s)Odds of live birth.Result(s)Our cohort included 10,615 patients with elevated an AMH level, including 2,707 patients with PCOS only. The adjusted odds of live birth per initiated cycle were significantly lower per each unit increase in the AMH level (odds ratio, 0.97; 95% confidence interval, 0.96–0.98). Increasing AMH level was associated with increased cancellation of fresh transfer (odds ratio, 1.12; 95% confidence interval, 1.10–1.15) up to an AMH level of 12 ng/mL. The decrease in the live birth rate appears to be caused by the increasing incidence of cancellation of fresh transfer because the live birth rate per completed transfer was maintained. Similar trends were observed in the PCOS and non-PCOS subanalyses.Conclusion(s)Among patients with AMH levels of ≥5 ng/mL undergoing fresh, autologous IVF, each unit increase in AMH level is associated with a 3% decrease in odds of live birth because of the increased incidence of fresh embryo transfer cancellation.

Survival outcomes following pregnancy or assisted reproductive technologies after breast cancer: A population-based study.

This study sought to determine the impact of pregnancy or assisted reproductive technologies (ART) on breast-cancer-specific survival among breast cancer survivors. The authors performed a cohort study using a novel data linkage from the California Cancer Registry, the California birth cohort, and the Society for Assisted Reproductive Technology Clinic Outcome Reporting System data sets. They performed risk-set matching in women with stages I-III breast cancer diagnosed between 2000 and 2012. For each pregnant woman, comparable women who were not pregnant at that point but were otherwise similar based on observed characteristics were matched at the time of pregnancy. After matching, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of pregnancy with breast-cancer-specific survival. We repeated these analyses for women who received ART. Among 30,021 women with breast cancer, 553 had a pregnancy and 189 attempted at least one cycle of ART. In Cox proportional hazards modeling, the pregnancy group had a higher 5-year disease-specific survival rate; 95.6% in the pregnancy group and 90.6% in the nonpregnant group (HR, 0.43; 95% CI, 0.24-0.77). In women with hormone receptor-positive cancer, we found similar results (HR, 0.43; 95% CI, 0.2-0.91). In the ART analysis, there was no difference in survival between groups; the 5-year disease-specific survival rate was 96.9% in the ART group and 94.1% in the non-ART group (HR, 0.44; 95% CI, 0.17-1.13). Pregnancy and ART are not associated with worse survival in women with breast cancer. We sought to determine the impact of pregnancy or assisted reproductive technologies (ART) among breast cancer survivors. We performed a study of 30,021 women by linking available data from California and the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. For each pregnant woman, we matched at the time of pregnancy comparable women who were not pregnant at that point but were otherwise similar based on observed characteristics. We repeated these analyses for women who received ART. We found that pregnancy and ART were not associated with worse survival.

Cumulative live birth rate in women aged ≤37 years after in vitro fertilization with or without preimplantation genetic testing for aneuploidy: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System retrospective analysis

ObjectiveTo investigate cumulative live birth rates (CLBRs) in cycles with and without preimplantation genetic testing for aneuploidy (PGT-A) among patients aged <35 and 35–37 years.DesignRetrospective cohort study.SettingSociety for Assisted Reproductive Technology reporting clinics.Patient(s)A total of 31,900 patients aged ≤ 37 years with initial oocyte retrievals between January 2014 and December 2015 followed through December 2016.Intervention(s)None.Main outcome measure(s)The primary outcome was CLBR among patients aged <35 and 35–37 years. The secondary outcomes included multifetal births, miscarriage, preterm birth, perinatal mortality, and the time to pregnancy resulting in a live birth. Adjusted odds ratios (aORs) adjusting for age, body mass index, total 2 pronuclei embryos, embryos transferred, and follow-up timeframe.Result(s)Among patients aged <35 years, PGT-A was associated with reduced CLBRs (70.6% vs. 71.1%; aOR, 0.82; 95% CI [confidence interval], 0.72–0.93). No association was found between PGT-A and CLBRs among patients aged 35–37 years (66.6% vs. 62.5%; aOR, 0.92; 95% CI, 0.83–1.01). Overall, there was no significant difference in the miscarriage rate (aOR, 0.97; 95% CI, 0.82–1.14). Multifetal birth rates were lower with PGT-A (9.5% vs. 23.1%); however, PGT-A was not an independent predictor of multifetal birth (aOR, 1.11; 95% CI, 0.91–1.36). The average time to pregnancy resulting in a live birth was 2.37 months (SD 3.20) for untested transfers vs. 4.58 months (SD 3.53) for PGT-A transfers.Conclusion(s)In women aged <35, the CLBR was lower with PGT-A than with the transfer of untested embryos. In women aged 35–37 years, PGT-A did not improve CLBRs.

The impact of single-step and sequential embryo culture systems on obstetric and perinatal outcomes in singleton pregnancies: the Massachusetts Outcomes Study of Assisted Reproductive Technology

To compare the obstetric and perinatal outcomes of deliveries conceived with embryos from single-step vs. sequential culture media systems. Historical cohort of Massachusetts vital records linked to assisted reproductive technology clinic data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System and laboratory embryology data from two large academic hospital fertility centers. Not applicable. Patients with singleton live birth deliveries between 2004 and 2017 conceived with autologous assisted reproductive technology cycles with fresh blastocyst transfer using either single-step (n = 1,058) or sequential (n = 474) culture media systems. None. Associations of single-step vs. sequential culture with obstetric outcomes (mode of delivery, placental abnormalities, pregnancy-induced hypertension, and gestational diabetes) and perinatal outcomes (preterm birth, low birthweight, small-for-gestational-age, and large-for-gestational-age [LGA]) were assessed with multivariate logistic modeling, adjusted for maternal age, race/ethnicity, education, parity, insurance type, protein supplementation, oxygen concentration, fertilization method, and number of transferred embryos. Compared with sequential culture, single-step culture was associated with increased odds of LGA (adjusted odds ratio 2.1, 95% confidence interval 1.04-4.22). There were no statistically significant differences between single-step and sequential culture media systems in the odds of placental abnormalities, pregnancy-induced hypertension, gestational diabetes, prematurity, small-for-gestational-age, or low birthweight. Single-step culture is associated with increased odds of LGA, indicating that embryo culture media systems may affect perinatal outcomes.