Autologous Assisted Reproductive Technology Cycles Research Articles

Age-Related Increase in Live-Birth Rates of First Frozen Thaw Embryo Compared With First Fresh Transfer in Initial Assisted Reproductive Technology Cycles Without Preimplantation Genetic Testing [ID 2683417

INTRODUCTION: Compare live-birth outcomes stratified by age between primary frozen (FET) and fresh transfers in initial autologous assisted reproductive technology (ART) cycles without preimplantation genetic testing (PGT). METHODS: This was a retrospective cohort study of autologous first ART cycles without PGT comparing success rates of primary embryo transfer (frozen thaw versus fresh) from the 2014–2020 SARTCORS database. We compared live-birth rate (LBR) stratified by age and cumulative live-birth rate (CLBR) for first FET versus first fresh cycles in first ART cycle. Primary transfer (FET or fresh) was the first transfer for an index retrieval. LBR was number of live births from first embryo transfer associated with first retrieval. CLBR was defined as at least one live birth from all linked embryo transfers within 1 year from initial retrieval. Multivariate logistic regression (MLR) determined association between live-birth outcomes and method of transfer. RESULTS: 228,171 first ART cycles resulted in primary embryo transfer. 62,100 initial FETs and 166,071 fresh transfers were compared. LBR was 48.3% for initial FETs versus 39.8% for initial fresh transfers (P<.001). CLBR was 71.8% for initial FETs versus 59.2% for initial fresh transfers (P<.001). MLR demonstrated that initial FETs had a greater chance of live birth across all age groups, with adjusted odds ratio of live birth incrementally increasing with advancing age groups. CONCLUSION: Overall, LBR and CLBR were greater for first FET than fresh transfers with incremental increases in odds of live birth with advancing age, suggesting the presence of a more favorable age-related change in endometrial receptivity present in frozen–thawed cycles.

The impact of insurance mandates on donor oocyte utilization: an analysis of 39,338 donor oocyte cycles from the Society for Assisted Reproductive Technology registry

A total of 19 states passed legislation mandating insurance coverage of assisted reproductive technology, and out-of-pocket costs associated with invitro fertilization vary significantly depending on the region. Consequently, it has been observed that assisted reproductive technology utilization differs regionally and is associated with the presence of an insurance mandate. However, it is unknown whether regional differences exist among patients using donor oocytes. This study aimed to determine the patient and cycle-specific parameters associated with the use of donor oocytes according to the insurance mandate status of the Society for Assisted Reproductive Technology clinic in which the assisted reproductive technology cycle was performed. This study was a retrospective cohort study using national data collected from the Society for Assisted Reproductive Technology registry for 39,338 donor oocyte cycles and 242,555 autologous oocyte cycles performed in the United States from January 1, 2014, to December 31, 2016. Cycles were stratified by insurance mandate of the state in which the assisted reproductive technology cycle was performed: comprehensive (coverage for at least 4 cycles of assisted reproductive technology), limited (coverage limited to 1-3 assisted reproductive technology cycles), offer (insurance mandates exist but exclude assisted reproductive technology treatment), and no mandate. The primary outcome was the number of previous autologous assisted reproductive technology cycles of the recipient. The secondary outcomes included age, serum follicle stimulating hormone level, frozen donor oocyte utilization, day of embryo transfer, number of embryos transferred, clinical pregnancy rate, and live birth rate. Analyses were adjusted for day of transfer, number of embryos transferred, and age of the recipient. Patients in no mandate states underwent fewer autologous assisted reproductive technology cycles (mean, 1.1; standard deviation, 1.6) before using donor oocytes than patients in offer (mean, 1.7; standard deviation, 2.5; P<.01), limited (mean, 1.5; standard deviation, 2.5; P<.01), and comprehensive (mean, 1.7; standard deviation, 2.0; P<.01) states. Patients in no mandate states were more likely to use frozen oocytes than patients in offer (relative risk, 0.54; 95% confidence interval, 0.52-0.57), limited (relative risk, 0.50; 95% confidence interval, 0.46-0.54), and comprehensive (relative risk, 0.94; 95% confidence interval, 0.89-0.99) states. Clinical pregnancy and live birth rates were similar among recipients of donor oocytes, regardless of insurance mandate. Despite similar ages and ovarian reserve parameters, patients without state-mandated insurance coverage of assisted reproductive technology were more likely to use frozen donor oocytes and undergo fewer autologous invitro fertilization cycles than their counterparts in partial or comprehensive insurance coverage states. These differences in donor oocyte utilization highlight the financial barriers associated with pursuing assisted reproductive technology in uninsured states.

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.

Female age is associated with the optimal number of oocytes to maximize fresh live birth rates: an analysis of 256,643 fresh ART cycles

Research questionWhat is the optimal number of oocytes retrieved at which maximum live birth rate is observed after fresh autologous assisted reproductive technology (ART) cycles for women of different ages? DesignRetrospective cohort study of all fresh autologous ART aspiration cycles (n = 256,643) undertaken in Australia and New Zealand between 2009 and 2015. Primary outcome measure was live birth rate (LBR) (delivery of at least one liveborn baby at 20 weeks’ gestation or over per fresh aspiration cycle). Cycles were grouped according to female age (<30, 30–34, 35–49, 40–44 and ≥45 years) and ovarian response (one to three, four to nine, 10–14, 15–19, 20–25 and ≥25 oocytes). Secondary outcome was incidence of ovarian hyperstimulation syndrome (OHSS) requiring hospitalization. ResultsAt different oocyte yields, LBR per fresh aspiration cycle peaked and then declined at, depending on female age: <30 years: six to 11 oocytes (LBR 31–34%); 30–34 years: 11–16 oocytes (LBR 29–30%); 35–39 years: nine to 17 oocytes (LBR 21–24%); and 40–44 years: 15–17 oocytes (LBR 11–12%). The incidence of OHSS increased significantly with the number of oocytes retrieved, from 1.2% with 15 oocytes retrieved to 9.3% with 30 or more oocytes retrieved (P < 0.001). ConclusionThe optimal number of oocytes at which maximum LBR was observed in a fresh aspiration cycle was highly dependent on age. Because of the observational nature of the results, a cause–effect relationship between the number of oocytes retrieved and LBR should not be assumed; evidence from well-designed randomized control trials is required before clinical advice can be suggested.

The impact of using donor sperm in assisted reproductive technology cycles on perinatal outcomes

To assess the impact of using donor sperm in assisted reproductive technology (ART) cycles on perinatal outcomes. Historical cohort study. US national database from the Society of Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 2012 to2013. Patients undergoing the first fresh autologous ART cycle using either donor or partner sperm. None. Miscarriage, preterm birth, low birthweight rates. A total of 134,710 fresh autologous ART cycles were evaluated from the SART CORS database. Following exclusion criteria and after restricting to the first cycle, 2,123 donor sperm and 42,799 partner sperm ART cycles were included in the final analyses. After adjusting for all confounding variables (including maternal age, race, body mass index, smoking status, gravidity, history of preterm birth, highest follicle stimulating hormone count, blastocyst transfer percentage, total embryo transferred, and etiology of infertility), no statistically significant differences in miscarriage rates, preterm births, very preterm births, low birthweight, and very low birthweight were observed. Birthweight was significantly lower in the partner sperm group than in the donor sperm group (3,292 ± 601 and 3,233 ± 592g in donor and partner sperm groups, respectively, adjusted P value 0.003); however, this small absolute difference (adjusted effect estimate 42g, 95% CI 14.7-70.9) does not carry clinical significance. The use of donor sperm in fresh autologous ART cycles was not associated with increased miscarriage, preterm births, or low birthweights, as compared to cycles using partner sperm. This information can be used in patient counseling to reassure patients using donor sperm in ART cycles.

Effect of race and ethnicity on utilization and outcomes of assisted reproductive technology in the USA

BackgroundThe purpose of this study was to determine the utilization and live birth rates of assisted reproductive technology (ART) modalities among various racial and ethnic groups in recent years.MethodsWe reviewed ART data reported to the Society for Assisted Reproductive Technologies Clinic Outcome Reporting System (SART CORS) for autologous ART and third-party ART (3ART) cycles which involved donor oocytes, sperm, embryos and gestational carrier, performed in the U.S. between 2004 and 2013. To gauge demand by various racial/ethnic groups for ART services, we examined fertility rates and demographics of the entire U.S. birth cohort over the same time interval.ResultsOf 1,132,844 autologous ART cycles 335,462 resulted in a live birth (29.6%). An additional, 217,030 3ART cycles resulted in 86,063 live births (39.7%). Hispanic and Black women demonstrated high fertility and lower utilization rates of autologous ART and 3ART. Caucasian and Asian women exhibited lower fertility rates and higher autologous ART and 3ART utilization. Autologous ART resulted in higher live birth rates among Caucasian and Hispanic women and lower rates among Asian and especially Black women. 3ART improved live birth rates in all races/ethnicities, though Black women experienced lower live birth rates with most modalities. Spontaneous abortion rates were higher among Black women following autologous ART and some 3ART modalities than those among Caucasian women.ConclusionUtilization of ART is inversely related to fertility rates. Autologous ART produces lower live birth rates among Asian and Black women. 3ART results in relatively low live birth rates among Black women.Trial registrationSART CORS #57, Registered 5/14/2015

CDC-reported assisted reproductive technology live-birth rates may mislead the public

The Centre for Disease Control and Prevention (CDC) publicly reports assisted reproductive technology live-birth rates (LBR) for each US fertility clinic under legal mandate. The 2014 CDC report excluded 35,406 of 184,527 (19.2%) autologous assisted reproductive technology cycles that involved embryo or oocyte banking from LBR calculations. This study calculated 2014 total clinic LBR for all patients utilizing autologous oocytes two ways: including all initiated assisted reproductive technology cycles or excluding banking cycles, as done by the CDC. The main limitation of this analysis is the CDC report did not differentiate between cycles involving long-term banking of embryos or oocytes for fertility preservation from cycles involving short-term embryo banking. Twenty-seven of 458 (6%) clinics reported over 40% of autologous cycles involved banking, collectively performing 12% of all US assisted reproductive technology cycles. LBR in these outlier clinics calculated by the CDC method, was higher than the other 94% of clinics (33.1% versus 31.1%). However, recalculated LBR including banking cycles in the outlier clinics was lower than the other 94% of clinics (15.5% versus 26.6%). LBR calculated by the two methods increasingly diverged based on proportion of banking cycles performed by each clinic reaching 4.5-fold, thereby, potentially misleading the public.

Are good patient and embryo characteristics protective against the negative effect of elevated progesterone level on the day of oocyte maturation?

To evaluate if an elevated progesterone (P) level on the day of human chorionic gonadotropin (hCG) administration is associated with a decrease in live-birth rate in patients with a good prognosis. Retrospective cohort study. Large, private, assisted reproductive technology (ART) practice. One thousand six hundred twenty fresh autologous ART cycles. None. Live-birth rate. A total of 934 blastocyst and 686 cleavage-stage embryo transfer (ET) cycles were evaluated. Serum P levels were not associated with markers of oocyte or embryo quality, including fertilization, embryo stage at transfer, and embryos available for cryopreservation. Patient age, stage of ET, embryo quality, the number of embryos transferred, and P level on the day of hCG administration were all significantly associated with live birth. Higher P levels were associated with decreased odds of live birth for cleavage- and blastocyst-stage embryos, poor-fair and good-quality embryos, and poor- and high-responder patients. The nonsignificance of interaction tests of P levels with embryo stage, embryo quality, patient age, and ovarian response indicated that the relationship between P level and live birth was similar regardless of these factors. An elevated serum P level on the day of hCG administration was negatively associated with live birth, even in ETs with a good prognosis.

Serum human chorionic gonadotropin levels on the day before oocyte retrieval do not correlate with oocyte maturity

To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. Retrospective cohort study. Military assisted reproductive technology (ART) program. Fresh autologous ART cycles. Serum hCG level the day before oocyte retrieval. Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful.

Conversion from assisted reproductive technology to intrauterine insemination in low responders: Is it advantageous?

To examine cycle outcomes among patients demonstrating an attenuated ovarian response that proceeded to oocyte retrieval to those converted to intrauterine insemination (IUI). Retrospective cohort study. Large private fertility center. First planned autologous assisted reproductive technology (ART) cycles among women demonstrating a poor ovarian response to hyperstimulation (≤4 follicles≥14 mm, peak E2<1,000 IU/L at hCG administration). Oocyte retrieval or IUI conversion. Live birth and clinical pregnancy. A total of 269 IUI conversions and 167 oocyte retrievals followed a poor ovarian response to gonadotropins among first planned ART cycles. Number of follicles≥14 mm (2.3 vs. 3.5) and peak E2 levels (555 vs. 743 pg/mL) were lower for IUI conversions compared with those proceeding to ART. Peak E2 was similar between groups after adjusting for follicle number (IUI: 611 pg/mL; ART: 652 pg/mL). Stimulation response was similar between treatment groups with equivalent follicle numbers. Undergoing oocyte retrieval was associated with significantly improved pregnancy (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.8-7.4) and live birth outcome (OR 3.5, 95% CI 1.7-8.0) after adjusting for age and follicle number. Among women demonstrating a poor ovarian response to gonadotropins, proceeding with planned ART resulted in significantly higher pregnancy rates than converting these cycles to IUI.

Microdose follicular flare: a viable alternative for normal-responding patients undergoing in vitro fertilization?

To compare cycle outcomes among normal-responding patients <or=30 years old receiving microdose follicular flare (MDF) and long-luteal agonist (LL). Retrospective cohort study. Military-based assisted reproductive technology (ART) center. First autologous ART cycles among 499 women <or=30 years old from January 1999 to December 2005. After oral contraceptive pill (OCP) administration before cycle start, patients were nonrandomly assigned to either LL or MDF for LH surge suppression. Patients in the LL group received 1 mg/day leuprolide acetate (LA) on cycle day 21, which was reduced to 0.25 mg/day 10-14 days later. Patients in the MDF group received LA (40 microg twice a day) beginning 3 days after discontinuing OCPs. Both groups received a combination of hMG and recombinant FSH. Primary outcomes were implantation, clinical pregnancy, and live-birth rates; in-cycle variables included peak E(2), oocytes retrieved, oocyte maturity, and fertilization rate. Multivariable models controlling for confounding by treatment indication found no significant differences between groups in implantation (MDF, 36%; LL, 38%), clinical pregnancy (MDF, 53%; LL, 56%), and live-birth rates (MDF, 47%; LL, 50%). No differences were observed in peak E(2), oocytes retrieved, oocyte maturity, fertilization rate, or embryos transferred. MDF use among normal-responding ART patients produced no differences in cycle outcome when compared with LL. Therefore, MDF may be a viable alternative for normal-responding patients.