Ethan Wantman

Cumulative birth rates with linked assisted reproductive technology cycles.

BACKGROUND Live-birth rates after treatment with assisted reproductive technology have traditionally been reported on a per-cycle basis. For women receiving continued treatment, cumulative success rates are a more important measure. METHODS We linked data from cycles of assisted reproductive technology in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for the period from 2004 through 2009 to individual women in order to estimate cumulative live-birth rates. Conservative estimates assumed that women who did not return for treatment would not have a live birth; optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment. RESULTS The data were from 246,740 women, with 471,208 cycles and 140,859 live births. Live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used. CONCLUSIONS Our results indicate that live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favorable patient and embryo characteristics. Live-birth rates among older women are lower than those among younger women when autologous oocytes are used but are similar to the rates among young women when donor oocytes are used. (Funded by the National Institutes of Health and the Society for Assisted Reproductive Technology.).

Calculating cumulative live-birth rates from linked cycles of assisted reproductive technology (ART): data from the Massachusetts SART CORS

OBJECTIVE To determine the feasibility of linking assisted reproductive technology (ART) cycles for individual women to compare per-cycle and cumulative live-birth rates. DESIGN Historical cohort study. SETTING Clinic-based data. PATIENT(S) A total of 27,906 ART cycles with residency or treatment in Massachusetts during 2004-2006 and reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) on-line database. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Per-cycle and cumulative live-birth rates. RESULT(S) Linkage of cycles up to and including the first live-birth delivery revealed 14,265 women who averaged 1.9+/-1.2 SD cycles (range 1-11). These cycles yielded 9,452 pregnancies resulting in 7,675 live-birth deliveries. From cycle 1 to cycle 4, the cumulative live-birth rate for all patients increased from 30.4% to 43.3%, 49.1%, and 51.9%, respectively, and plateaued thereafter at about 53%. The cumulative live-birth rate after three cycles using donor oocytes was approximately 60% for women aged<43 years and >50% for women>or=43 years; for autologous oocytes it was 60.1% for ages<35 years and declined steadily to 8.5% for ages>or=43 years. CONCLUSION(S) The results demonstrate the feasibility of linking ART cycles for individual women from SART CORS to characterize cumulative live-birth rates.

Factors associated with monozygosity in assisted reproductive technology pregnancies and the risk of recurrence using linked cycles

OBJECTIVE To evaluate factors associated with monozygosity (MZ) (number of fetal heartbeats on early ultrasound greater than the number of embryos transferred) and the risk of recurrence in subsequent pregnancies using a national assisted reproduction database. DESIGN Historical cohort study. SETTING Clinic-based data. PATIENT(S) 197,327 pregnancies (including 2,824 with evidence of MZ) from cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) between 2004 and 2010. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Evidence of MZ, adjusted odds ratios and their 95% confidence intervals computed from logistic regression models. RESULT(S) In the univariate analysis, the risk of MZ was increased with ovulation disorders, donor oocytes, gonadotropin-releasing hormone agonist (GnRH-a) suppression, assisted hatching (AZH), and day 5-6 transfer, and was decreased with higher follicle-stimulating hormone (FSH) doses (≥3,000 IU). In the multivariate analysis, the risk of MZ was increased with GnRH-a suppression, AZH, and decreased with intracytoplasmic sperm injection (ICSI) and higher FSH dose. The interaction showed that although MZ was more likely with day 5-6 embryos, AZH had a minimal nonsignificant effect, whereas in day 2-3 embryos, AZH had a substantial statistically significant effect. Only one woman had a recurrence of MZ in a subsequent assisted reproduction pregnancy, which is consistent with randomness. CONCLUSION(S) The risk of MZ was higher with fresh day 5-6 embryos, donor oocytes, GnRH-a suppression, lower FSH doses, and AZH (particularly with day 2-3 embryos).

Use of preimplantation genetic diagnosis and preimplantation genetic screening in the United States: a Society for Assisted Reproductive Technology Writing Group paper.

OBJECTIVE To comprehensively report Society for Assisted Reproductive Technology (SART) member program usage of preimplantation genetic testing (PGT), preimplantation genetic diagnosis (PGD) for diagnosis of specific conditions, and preimplantation genetic screening for aneuploidy (PGS). DESIGN Retrospective study. SETTING United States SART cohort data. PATIENT(S) Women undergoing a PGT cycle in which at least one embryo underwent biopsy. INTERVENTION(S) PGT. MAIN OUTCOME MEASURE(S) PGT use, indications, and delivery rates. RESULT(S) Of 190,260 fresh, nondonor assisted reproductive technology (ART) cycles reported to SART CORS in 2007-2008, 8,337 included PGT. Of 6,971 cycles with a defined indication, 1,382 cycles were for genetic diagnosis, 3,645 for aneuploidy screening (PGS), 527 for translocation, and 1,417 for elective sex election. Although the total number of fresh, autologous cycles increased by 3.6% from 2007 to 2008, the percentage of cycles with PGT decreased by 5.8% (4,293 in 2007 and 4,044 in 2008). As a percentage of fresh, nondonor ART cycles, use dropped from 4.6% (4,293/93,433) in 2007 to 4.2% (4,044/96,827) in 2008. The primary indication for PGT was PGS: cycles performed for this indication decreased (-8.0%). PGD use for single-gene defects (+3.2%), elective sex selection (+5.3%), and translocation analysis (+0.5%) increased. PGT usage varied significantly by geographical region. CONCLUSION(S) PGT usage in the United States decreased between 2007 and 2008 owing to a decrease in PGS. Use of elective sex selection increased. High transfer cancellation rates correlated with reduced live-birth rates for some PGT indications.

Increased risk of large-for-gestational age birthweight in singleton siblings conceived with in vitro fertilization in frozen versus fresh cycles

BackgroundChildren born from fresh in vitro fertilization (IVF) cycles are at greater risk of being born smaller and earlier, even when limited to singletons; those born from frozen cycles have an increased risk of large-for-gestational age (LGA) birthweight (z-score ≥1.28). This analysis sought to overcome limitations in other studies by using pairs of siblings, and accounting for prior cycle outcomes, maternal characteristics, and embryo state and stage.MethodsPairs of singleton births conceived with IVF and born between 2004 and 2013 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database, matched for embryo stage (blastocyst versus non-blastocyst) and infant gender, categorized by embryo state (fresh versus frozen) in 1st and 2nd births (four groups).ResultsThe data included 7795 singleton pairs. Birthweight z-scores were 0.00–0.04 and 0.24–0.26 in 1st and 2nd births in fresh cycles, and 0.25–0.34 and 0.50–0.55 in frozen cycles, respectively. LGA was 9.2–9.8 and 14.2–15.4% in 1st and 2nd births in fresh cycles, and 13.1–15.8 and 20.8–21.0% in 1st and 2nd births in frozen cycles. The risk of LGA was increased in frozen cycles (1st births, adjusted odds ratios (AOR) 1.74, 95% CI 1.45, 2.08; and in 2nd births when the 1st birth was not LGA, AOR 1.70, 95% CI 1.46, 1.98 for fresh/frozen and 1.40, 1.11, 1.78 for frozen/frozen).ConclusionsOur results with siblings indicate that frozen embryo state is associated with an increased risk for LGA. The implications of these findings for childhood health and risk of obesity are unclear, and warrant further investigation.

Society for Assisted Reproductive Technology and assisted reproductive technology in the United States: a 2016 update

The Society for Assisted Reproductive Technology (SART) was established within a few years of assisted reproductive technology (ART) in the United States, and has not only reported on the evolution of infertility care, but also guided it toward improved success and safety. Moving beyond its initial role as a registry, SART has expanded its role to include quality assurance, data validation, practice and advertising guidelines, research, patient education and advocacy, and membership support. The success of ART in this country has greatly benefited from SARTs role, as highlighted by a series of graphs. SART continues to set the standard and lead the way.

Application of a validated prediction model for in vitro fertilization: comparison of live birth rates and multiple birth rates with 1 embryo transferred over 2 cycles vs 2 embryos in 1 cycle

OBJECTIVE The purpose of this study was to use a validated prediction model to examine whether single embryo transfer (SET) over 2 cycles results in live birth rates (LBR) comparable with 2 embryos transferred (DET) in 1 cycle and reduces the probability of a multiple birth (ie, multiple birth rate [MBR]). STUDY DESIGN Prediction models of LBR and MBR for a woman considering assisted reproductive technology developed from linked cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System for 2006-2012 were used to compare SET over 2 cycles with DET in 1 cycle. The prediction model was based on a womans age, body mass index (BMI), gravidity, previous full-term births, infertility diagnoses, embryo state, number of embryos transferred, and number of cycles. RESULTS To demonstrate the effect of the number of embryos transferred (1 or 2), the LBRs and MBRs were estimated for women with a single infertility diagnosis (male factor, ovulation disorders, diminished ovarian reserve, and unexplained); nulligravid; BMI of 20, 25, 30, and 35 kg/m2; and ages 25, 35, and 40 years old by cycle (first or second). The cumulative LBR over 2 cycles with SET was similar to or better than the LBR with DET in a single cycle (for example, for women with the diagnosis of ovulation disorders: 35 years old; BMI, 30 kg/m2; 54.4% vs 46.5%; and for women who are 40 years old: BMI, 30 kg/m(2); 31.3% vs 28.9%). The MBR with DET in 1 cycle was 32.8% for women 35 years old and 20.9% for women 40 years old; with SET, the cumulative MBR was 2.7% and 1.6%, respectively. CONCLUSION The application of this validated predictive model demonstrated that the cumulative LBR is as good as or better with SET over 2 cycles than with DET in 1 cycle, while greatly reducing the probability of a multiple birth.

A prediction model for live birth and multiple births within the first three cycles of assisted reproductive technology.

OBJECTIVE To develop a model predictive of live-birth rates (LBR) and multiple birth rates (MBR) for an individual considering assisted reproduction technology (ART) using linked cycles from Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) for 2004-2011. DESIGN Longitudinal cohort. SETTING Clinic-based data. PATIENT(S) 288,161 women with an initial autologous cycle, of whom 89,855 did not become pregnant and had a second autologous cycle and 39,334 did not become pregnant in the first and second cycles and had a third autologous cycle, with an additional 33,598 women who had a cycle using donor oocytes (first donor cycle). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) LBRs and MBRs modeled by womans age, body mass index, gravidity, prior full-term births, infertility diagnoses by oocyte source, fresh embryos transferred, and cycle, using backward-stepping logistic regression with results presented as adjusted odds ratios (AORs) and 95% confidence intervals. RESULT(S) The LBRs increased in all models with prior full-term births, number of embryos transferred; in autologous cycles also with gravidity, diagnoses of male factor, and ovulation disorders; and in donor cycles also with the diagnosis of diminished ovarian reserve. The MBR increased in all models with number of embryos transferred and in donor cycles also with prior full-term births. For both autologous and donor cycles, transferring two versus one embryo greatly increased the probability of a multiple birth (AOR 27.25 and 38.90, respectively). CONCLUSION(S) This validated predictive model will be implemented on the Society for Assisted Reproductive Technology Web site (www.sart.org) so that patients considering initiating a course of ART can input their data on the Web site to generate their expected outcomes.

Cycle 1 as predictor of assisted reproductive technology treatment outcome over multiple cycles: an analysis of linked cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System online database.

OBJECTIVE To determine whether the first cycle of assisted reproductive technology (ART) predicts treatment course and outcome. DESIGN Retrospective study of linked cycles. SETTING Society for Assisted Reproductive Technology Clinic Outcome Reporting System database. PATIENT(S) A total of 6,352 ART patients residing or treated in Massachusetts with first treatment cycle in 2004-2005 using fresh, autologous oocytes and no prior ART. Women were categorized by first cycle as follows: Group I, no retrieval; Group II, retrieval, no transfer; Group III, transfer, no embryo cryopreservation; Group IV, transfer plus cryopreservation; and Group V, all embryos cryopreserved. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Cumulative live-birth delivery per woman, use of donor eggs, intracytoplasmic sperm injection (ICSI), or frozen embryo transfers (FET). RESULT(S) Groups differed in age, baseline FSH level, prior gravidity, diagnosis, and failure to return for Cycle 2. Live-birth delivery per woman for groups I through V for women with no delivery in Cycle I were 32.1%, 35.9%, 40.1%, 53.4%, and 51.3%, respectively. Groups I and II were more likely to subsequently use donor eggs (14.5% and 10.9%). Group II had the highest use of ICSI (73.3%); Group III had the lowest use of FET (8.9%). CONCLUSION(S) Course of treatment in the first ART cycle is related to different cumulative live-birth delivery rates and eventual use of donor egg, ICSI, and FET.

Second try: who returns for additional assisted reproductive technology treatment and the effect of a prior assisted reproductive technology birth

OBJECTIVE To evaluate the effect of a prior assisted reproductive technology (ART) live birth on subsequent live-birth rates. DESIGN Historical cohort study. SETTING Clinic-based data. PATIENT(S) The study population included 297,635 women with 549,278 cycles from 2004 to 2010 from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Try 1 refers to ART cycles up to and including the first live birth, try 2 to ART cycles after a first live birth. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Live-birth rates by cycle number, try number, and oocyte source. RESULT(S) Younger women at try 1 are more likely to return for try 2. Women returning for try 2 were more likely to have had an ART singleton versus multiple birth (33.2% after a try 1 singleton versus 8.1% after twins and 4.9% after triplets) and were less likely to have a diagnosis of diminished ovarian reserve or tubal factors. Live-birth rates were significantly higher for try 2 compared with try 1 for autologous fresh cycles, averaging 7.7 percentage points higher over five cycles. Live-birth rates were not significantly different for try 2 versus try 1 with thawed autologous cycles or either fresh or thawed donor cycles. CONCLUSION(S) These results indicate that when fresh autologous oocytes can be used, live-birth rates per cycle are significantly greater after a prior history of an ART live birth.