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Original Investigation |

Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles

Andrew D. A. C. Smith, PhD1,2; Kate Tilling, PhD1,2; Scott M. Nelson, PhD3; Debbie A. Lawlor, PhD1,2
[+] Author Affiliations
1Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom
2School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
3School of Medicine, University of Glasgow, Glasgow, United Kingdom
JAMA. 2015;314(24):2654-2662. doi:10.1001/jama.2015.17296.
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Importance  The likelihood of achieving a live birth with repeat in vitro fertilization (IVF) is unclear, yet treatment is commonly limited to 3 or 4 embryo transfers.

Objective  To determine the live-birth rate per initiated ovarian stimulation IVF cycle and with repeated cycles.

Design, Setting, and Participants  Prospective study of 156 947 UK women who received 257 398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed up until June 2012.

Exposures  In vitro fertilization, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers.

Main Outcomes and Measures  Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted, and conservative cumulative live-birth rates were estimated, reflecting 0%, 30%, and 100%, respectively, of women who discontinued due to poor prognosis and having a live-birth rate of 0 had they continued.

Results  Among the 156 947 women, the median age at start of treatment was 35 years (interquartile range, 32-38; range, 18-55), and the median duration of infertility for all 257 398 cycles was 4 years (interquartile range, 2-6; range, <1-29). In all women, the live-birth rate for the first cycle was 29.5% (95% CI, 29.3%-29.7%). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth cycle, with 65.3% (95% CI, 64.8%-65.8%) of women achieving a live birth by the sixth cycle. In women younger than 40 years using their own oocytes, the live-birth rate for the first cycle was 32.3% (95% CI, 32.0%-32.5%) and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (95% CI, 67.8%-68.9%). For women aged 40 to 42 years, the live-birth rate for the first cycle was 12.3% (95% CI, 11.8%-12.8%), with 6 cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (95% CI, 29.7%-33.3%). For women older than 42 years, all rates within each cycle were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower for women with untreated male partner–related infertility compared with those with any other cause, but treatment with either intracytoplasmic sperm injection or sperm donation removed this difference.

Conclusions and Relevance  Among women in the United Kingdom undergoing IVF, the cumulative prognosis-adjusted live-birth rate after 6 cycles was 65.3%, with variations by age and treatment type. These findings support the efficacy of extending the number of IVF cycles beyond 3 or 4.

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Figures

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Figure 1.
Definition of Eligible and Analysis Cohort

IVF indicates in vitro fertilization.

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Figure 2.
Cumulative Live-Birth Rate Across All Initiated IVF Cycles by Age and Oocyte Source

The prognosis-adjusted estimate of cumulative live-birth rate (ie, the rate shown on the y-axis is the likelihood of a live birth across all initiated cycles up to and including the numbers on the x-axis), with 95% confidence intervals (error bars). These are presented for women in 2 different age categories at the start of their first in vitro fertilization (IVF) treatment cycle (<40 years and 40-42 years; women in both of these categories used their own oocytes) and also in women who used donor oocytes (these women cover the full age range). Data for women older than 42 years at their first treatment cycle are not shown because rates were so low it would have been difficult to represent them on this same graph (full results for these women are shown in Table 3). The prognostic-adjusted estimate assumes that 30% of those who discontinued IVF did so because of poor prognosis and that the live-birth rate in that 30% would have been 0 had they continued. Analyses were completed for 156 947 women undergoing 257 398 cycles. Log-rank tests indicated a difference between the cumulative live-birth rates for all groups (P < .001 for all comparisons).

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Figure 3.
Cumulative Live-Birth Rate Across All Initiated IVF Cycles by ICSI and Sperm Donation

The prognosis-adjusted estimates of cumulative live-birth rates (ie, the rate shown on the y-axis is the likelihood of a live birth across all initiated cycles up to and including the numbers on the x-axis), with 95% confidence intervals (error bars). These are shown for couples without a male-partner cause of infertility, couples with a male cause who were not treated with intracytoplasmic sperm injection (ICSI) or sperm donation, those with a male cause who were treated with ICSI, and those with a male cause who used sperm donation. The prognostic-adjusted estimate assumes that 30% of those who discontinued in vitro fertilization (IVF) did so because of poor prognosis and that the live-birth rate in that 30% would have been 0 had they continued. Analyses were completed for 156 947 women undergoing 257 398 cycles. Log-rank tests indicated a difference between the cumulative live-birth rates for all groups (P < .001 for all comparisons).

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Figure 4.
Live-Birth Rate Within Each Single In Vitro Fertilization Treatment Cycle by Oocyte Retrieval in First Cycle

The live-birth rate within each individual first, second, and third treatment cycle (ie, for each curve, the rate on the y-axis is the rate for just that 1 treatment cycle) according to the number of oocytes retrieved in the first treatment cycle. Analyses are for 134 903 women younger than 40 years using their own oocytes. Box and whiskers indicate the central 95% of the distribution of oocytes retrieved in the first cycle, as well as the median and lower and upper quartiles.

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