Costs of achieving live birth from assisted reproductive technology: a comparison of sequential single and double embryo transfer approaches.

A total of 14,398 fresh ART cycles resulting in ET among patients younger than 35 years of age with no prior ART cycles and cryopreservation of at least one embryo were started in 2012. Among these cycles, 4,129 (28.7%) were eSET and 10,001 (69.5%) were elective DET. Patient and cycle characteristics of eSET and DET groups differed significantly with regard to ART diagnosis and cycle characteristics, although the magnitude of most differences was relatively small ( Table 1 ). Compared with the DET group, the eSET group had a lower percentage of transfers among patients with diminished ovarian reserve (4.3% vs. 6.4%), endometriosis (8.8% vs. 12.2%), tubal factor infertility (13.9% vs. 16.0%), and male factor infertility (38.4% vs. 41.8%), but a higher percentage among patients with some other (11.8% vs. 9.0%) or unexplained (17.8% vs. 14.5%) reason for ART. The eSET group had a higher percentage of retrievals of 20 or more oocytes (36.1% vs. 29.4%) and a higher percentage of transfers using preimplantation genetic diagnosis (5.9% vs. 3.3%) than the DET group, but a lower percentage of transfers using assisted hatching (13.1% vs. 23.9%) or intracytoplasmic sperm injection (ICSI) (68.9% vs. 78.0%). The eSET group had a larger percentage of blastocyst transfers (90.1% vs. 68.6%) than the DET group and a larger percentage of transfers cryopreserving six or more embryos (32.3% vs. 23.2%). The 10,001 DET cycles performed in 2012 yielded total estimated ART treatment costs of $157.2 million ( Fig. 1 ). These cycles resulted in 3,300 (33.0%) singleton, 2,399 (24.0%) twin, and 70 (0.7%) triplet or higher-order live births, with estimated total pregnancy/infant-associated medical costs of $423.8 million. Total estimated costs were $580.9 million, or $58,087 per fresh cycle. The 10,001 DET cycles performed in 2012 resulted in a live birth rate of 57.7% and a multiple live birth rate of 24.7%. The estimated total number of live born infants was 8,308. Live birth rates for sequential SET cycles started in 2012 were calculated to project costs and birth outcomes for the DET cycles if they had been performed instead as sequential SETs ( Fig. 2 ). Of the 4,129 fresh, autologous eSET cycles started in 2012, 49.2% resulted in singleton live births, approximately 1.0% in twin live births, and approximately 0.1% in triplet or higher-order live births. Of those that did not achieve a live birth, 698 (34.0%) attempted a frozen SET. For the frozen cycles, 35.2% resulted in a singleton live birth, approximately 0.4% resulted in a twin live birth, and none resulted in a triplet or higher-order live birth. If the 10,001 DET cycles performed in 2012 had instead been performed as sequential SET, the estimated ART treatment costs for the fresh eSET would have been identical to the ART treatment costs for DET, at $157.2 million ( Fig. 3 ). However, because 49.8% of eSET cycles in 2012 did not result in a live birth, we would expect 4,978 additional frozen ETs. The frozen cycles would have cost an additional $19.0 million, for total projected ART treatment costs of $176.1 million. Given the success rates seen for sequential SET in Figure 2 , we would expect 49.2% of the 10,001 fresh eSET cycles to result in singleton live births (n = 4,922), 1.0% in twin live births (n = 96), 0.1% in triplet or higher-order live births (n = 7), and 49.8% (n = 4,978) to not have resulted in a live birth. Assuming that all 4,978 patients without a live birth would undergo an additional frozen SET, we would expect 35.2% to result in singleton live births (n = 1,755), 0.4% in twin live births (n = 18), and no triplet or higher-order live births. The total projected pregnancy/infant-associated medical costs for births resulting from sequential SET would have been $209.8 million. If the 10,001 DET cycles performed in 2012 had been performed as sequential SET, the total estimated ART treatment and pregnancy/infant-associated medical costs would have been $386.0 million rather than the $580.9 million estimated for DET, yielding an estimated savings of $195.0 million, or a 34% reduction in costs. The average total cost per fresh cycle would have been approximately $38,600, as compared with $58,100 for DET. The hypothetical 10,001 sequential SET cycles would have resulted in an estimated 6,798 live births, of which 121 would have been multiple live births, for a projected cumulative live birth rate of 68.0% and a projected cumulative multiple live birth rate of 1.2%. The estimated total number of infants born would have been 6,926. When we restricted our analysis to blastocyst transfers among patients who retrieved at least 15 oocytes and cryopreserved at least three embryos, results were similar (data not shown). For 3,117 DET cycles performed in 2012, the live birth rate was 60.8%, the multiple live birth rate was 29.1%, and the total estimated ART treatment and pregnancy/infant-associated medical costs were $199.8 million, or $64,093 per fresh cycle. Had the cycles been performed as sequential SET, the estimated live birth rate would have been 70.4%, the estimated multiple live birth rate 1.6%, and the estimated total costs $122.6 million, or $39,342 per fresh cycle.

Although sequential SET among women younger than 35 years of age who are undergoing their first ART cycle results in higher treatment costs compared with DET ($176.1 million vs. $157.2 million), estimates from this analysis show pregnancy/infant-associated medical costs to be markedly lower ($209.8 million vs. $423.8 million), resulting in lower overall costs ($386.0 million vs. $580.9 million). These cost savings are achieved while increasing overall live birth rates (57.7% for DET and 68.0% for sequential SET) due to a reduction in multiple birth rates (24.7% for DET and 1.2% for sequential SET). For this population of women, sequential SET rather than DET would result in lower total costs, for a potential savings of $195.0 million in 2012. The 10,001 DET cycles included in the present study represent only 12.4% of all fresh autologous transfers performed in 2012; however, the projected decrease of 2,348 multiple births accounts for 29.3% of multiple births resulting from all fresh autologous transfers performed in 2012. The multiple birth rate for all 80,783 fresh autologous transfers performed in 2012 was 9.9%. If 10,001 of these transfers had been performed as sequential SET, the multiple birth rate would have been only 7.0% ( 12 ). These results align with other studies that have found cumulative live birth rates for two SETs to be at least as high as live birth rates for one DET ( 16 – 18 ) and two SETs to be more cost effective than one DET ( 19 – 21 ). These studies were small in size compared with our study or did not explore both birth rates and costs. The present study shows an opportunity for cost savings among patients younger than 35 years of age who are having their first ART cycle with additional embryos available for transfer if SETs rather than DETs are performed. These cost savings could be even higher if patients meeting less stringent criteria—such as good prognosis patients 35–37 years of age—are considered for sequential SET ( 9 , 22 ). A barrier to realizing this potential savings is that ART treatment costs in the United States are typically paid by the patient, whereas most pregnancy/infant-associated medical costs are typically paid by an insurer. Currently, only eight states mandate insurance coverage for ART procedures, and coverage in these states varies widely ( 23 ). The potential for increased ART treatment costs may dissuade ART patients from selecting sequential SET instead of DET. Had insurance covered ART treatment costs in addition to pregnancy/infant-associated medical costs in 2012—and required sequential SET as a condition for coverage—our estimates suggest a $37.8 million savings versus what was actually spent on just pregnancy/infant-associated medical costs for DET cycles performed in 2012, despite the increased cost for ART treatment. Although these numbers indicate a savings with insurance coverage of ART treatment when a limited number of embryos are transferred, our analysis does not take into account the additional cost of providing ART treatment to patients who do not meet the good prognosis criteria or the additional treatment and medical costs that would arise from an increase in ART use as a result of ART treatment coverage ( 24 – 26 ). It also assumes that insurance is paying all of the pregnancy/infant-associated medical costs, when a portion of these costs are likely paid by the patient. An alternative mechanism for encouraging sequential SET would be incentives offered by the ART treatment provider, such as a discounted rate on additional frozen cycles, if needed after a fresh eSET, or package pricing for sequential SET cycles. This study has several limitations. First, when calculating projected costs for DET performed as sequential SET, we assumed that the DET group would experience the same success rates as the sequential SET group. Differences in characteristics between the eSET and DET groups could result in the DET group experiencing lower success rates if attempting eSET instead. However, a subanalysis of cycles that were more similar between the eSET and DET groups in some of these characteristics did not affect results. Second, this study does not take into account the increased potential for patient dropout when performing two cycles instead of one. Third, this study does not take into account the reduction in total infants born and the additional ART treatment and pregnancy/infant-associated medical costs that would be incurred for patients who want additional children but birthed fewer infants as a result of choosing sequential SET. Fourth, the medical cost estimates include only direct medical costs through the first year of life, not nonmedical costs (e.g., educational intervention programs) or costs beyond the first year. Finally, these cost estimates do not take into account that singletons born after DET generally have lower birth weights and earlier gestational ages than singletons born after eSET ( 27 , 28 ), thus requiring more medical intervention. As a result, these estimates may underestimate the cost savings. This study demonstrates that the use of sequential SET rather than DET during ART can produce overall cost savings. More important, this approach can improve perinatal outcomes among children conceived through ART and reduce morbidity among their mothers by reducing multiple births and their sequelae. However, the mechanism for transitioning patients from DET to sequential SET is unclear because patients are typically responsible for paying ART treatment costs in the United States. Other countries, such as Canada and Belgium, have provided public funding for ART treatments in exchange for a SET requirement in good prognosis patients ( 26 , 29 , 30 ).

We used data from the Centers for Disease Control and Prevention’s National ART Surveillance System, which contains ART cycle characteristics, patient characteristics, and treatment and pregnancy outcomes for >97% of all ART cycles performed in the United States ( 12 ). Our analysis included all fresh, autologous eSETs or elective DETs performed in 2012 among patients who were good candidates for eSET, defined as those younger than 35 years of age with no previous ART treatment ( 13 ). Because the number of embryos available for transfer is not collected in the National ART Surveillance System, we classified a transfer as elective if at least one embryo was cryopreserved. For fresh autologous transfers among patients younger than 35 years of age with no previous ART cycles who used eSET but did not achieve a live birth, we also analyzed the first frozen SET occurring after the failed first fresh eSET. The frozen cycle had to occur within 1 year of the fresh cycle. Undergoing a fresh eSET and then a frozen SET, if needed, is hereafter referred to as “sequential SET.” Patient and cycle characteristics were compared between fresh eSET and fresh elective DET cycles. Patient characteristics included demographics, pregnancy history, and infertility diagnosis. Cycle characteristics included the number of oocytes retrieved, embryo manipulation techniques used, day of ET, and cryopreservation. The χ 2 tests, with an adjustment for clustering of cycles by ART clinic, were conducted to determine statistically significant differences in characteristics between the two groups. Chambers et al. ( 14 ) reported the cost of a fresh transfer cycle to be $12,513 and the cost of a frozen cycle to be $3,035 in 2006 US dollars. We assumed average ART treatment costs to be $15,715 per fresh cycle and $3,812 per frozen cycle after converting costs to 2012 US dollars and adjusting costs according to the Consumer Price Index for All Urban Consumers for Medical care services ( 15 ). The ART treatment costs include all costs before achieving pregnancy, such as stimulation, retrieval, embryology, transfer, and cryopreservation. Lemos et al. ( 11 ) reported average pregnancy/infant-associated medical costs for an ART birth to be $26,922 per singleton, $115,238 per twin, and $434,668 per triplet or higher-order live birth in 2010 US dollars. We assumed average pregnancy/infant-associated medical costs to be $28,829 per singleton, $123,402 per twin, and $465,464 per triplet or higher-order live birth after converting costs to 2012 US dollars and adjusting costs according to the Consumer Price Index for All Urban Consumers for Medical care services ( 15 ). Medical cost estimates include all payments made by private insurers or patients for maternal costs from 27 weeks before delivery to 1 month after delivery and for infant costs through the first year of life among commercially insured women 19–45 years of age. We estimated total ART treatment and pregnancy/infant-associated medical costs for the 10,001 DET cycles started in 2012 by multiplying the number of ART transfers and births by average treatment and medical costs. We calculated live birth rates as the number of live births per number of fresh DET, multiplied by 100. We estimated the number of live-born infants by assuming that no infants were stillborn in a multiple birth, rather than reporting the actual number of live-born infants for these cycles, for comparability with projected numbers. We projected ART treatment and pregnancy/infant-associated medical costs for the DET cycles started in 2012 by assuming that they had been performed as sequential SET cycles. We calculated live birth rates for the actual number of sequential SET cycles started in 2012 and used these rates to project the number of transfers and births. We multiplied the projected number of transfers and births by the average treatment and medical costs to estimate total ART treatment and pregnancy/infant-associated medical costs. We calculated live birth rates as the number of live births per number of fresh eSET, multiplied by 100. We estimated the number of live-born infants by assuming that no infants were stillborn in a multiple birth. We conducted a subanalysis to make the sequential SET and DET groups more comparable. All analyses were repeated among patients who had at least 15 oocytes retrieved, did a blastocyst transfer, and cryopreserved at least three embryos. For the number of live births among cycles started in 2012, we suppressed any numbers 1–4 to protect patient confidentiality, reporting instead the possible range 1 ≤ n ≤ 4. We also suppressed any numbers that would allow the suppressed number to be calculated. We used an average live birth rate for these suppressed numbers by taking the average of all possible live birth rates for all possible values of n . This study was approved by the Center for Disease Control and Prevention’s Institutional Review Board.