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

Abstract

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.

Figure 1. Definition of eligible and analysis cohort.

Figure 2. Cumulative live-birth rate across all initiated IVF cycles by age and oocyte source.

The figure shows the prognosis-adjusted estimates of cumulative live-birth rates (i.e. 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. These are presented for women in two different age categories at the start of their first 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 aged over 42 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 zero had they continued. Analyses were completed in 156,947 women undergoing 257,398 cycles. Log-rank tests indicated a difference between the cumulative live-births rates for all groups (p < 0.001 for all comparisons).

Figure 3. Cumulative live-birth rate across all initiated IVF cycles by ICSI and sperm donation.

The figure shows the prognosis-adjusted estimates of cumulative live-birth rates (i.e. 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. These are shown for couples without a male cause of infertility, couples with a male cause who were not treated with 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 IVF did so because of poor prognosis and that the live-birth rate in that 30% would have been zero had they continued. Analyses were completed in 156,947 women undergoing 257,398 cycles. Log-rank tests indicated a difference between the cumulative live-births rates for all groups (p < 0.001 for all comparisons).

Figure 4. Live-birth rate within each single IVF treatment cycle by oocyte retrieval in first cycle.

The figure shows the live-birth rate within each individual first, second and third treatment cycle (i.e. for each line the rate on the y-axis is the rate for just that one treatment cycle), against the number of oocytes retrieved in the first treatment cycle (shown on the x-axis). Analyses are in 134,903 women aged less than 40 years and using their own oocytes. Box and whiskers show the central 95% of the distribution of oocytes retrieved in the first cycle, as well as the median and lower and upper quartiles.