IVF Study Estimates Overall Chance of Pregnancy

Yael Waknine

June 28, 2012

June 28, 2012 — Although many statistics on in vitro fertilization (IVF) focus on the number of pregnancies per cycle, a new study published in the June 28 issue of the New England Journal of Medicine sheds light on the chance for live birth during an entire treatment course.

Barbara Luke, ScD, MPH, from the Department of Obstetrics, Gynecology, and Reproductive Biology at Michigan State University, East Lansing, and colleagues found that 3 consecutive IVF cycles using a woman's own eggs can yield live birth rates as high as 74.6% in the context of favorable patient and embryo characteristics.

Factors associated with greater success included maternal age of less than 31 years, use of blastocyst embryos, and transfer of 2 embryos rather than 1.

In older women, use of donor eggs can dramatically increase the chance of success to more than 80%, particularly when fresh rather than frozen embryos are used.

"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," the authors write.

"The study is important because it is a reflection of patients' real concerns; namely, 'What is my overall chance of getting pregnant?' " emphasized Daniel B. Shapiro, MD, from Reproductive Biology Associates in Atlanta, Georgia, in an interview with Medscape Medical News.

The findings are valuable for a number of reasons, according to Dr. Shapiro, who was not involved in the work. "First, it gives patients realistic data regarding the chance of having a baby within 'x' number of tries. Second, it allows for meaningful cost analysis on a per patient basis. Put another way, clinics can use this kind of data to tell a patient the average total cost per baby born. Third, cumulative data reporting allows clinics to identify patients who should continue and those who are best served by abandoning therapy [earlier] in a treatment course," he said.

Dr. Shapiro noted that limitations to this type of evaluation include lack of accounting for the emotional burden associated with continued attempts, as well as myriad third-party compensation plans that allow some to continue "ad infinitum" and limit others to a single try.

Dr. Shapiro is board-certified in both obstetrics and gynecology and reproductive endocrinology/infertility. He is a member of the American Society for Reproductive Medicine, the American College of Obstetrics and Gynecology, and the Society of Reproductive Endocrinologists.

Data From 250,000 American Women

For the study, researchers examined data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for 246,740 women undergoing IVF from 2004 to 2009. By the end of the research period, 140,859 babies were born out of 471,208 IVF cycles.

Live birth rates were estimated in 2 ways: a "conservative analysis" based on the assumption that none of the women who did not return for a subsequent cycle would have had a live birth, and an "optimal analysis" in which these women would have had the same birth rates as those who did return.

The highest birth rates occurred in women younger than 31 years of age. After 3 IVF cycles, the conservative analysis estimated that 63.3% would have had a baby; the optimal analysis was 74.6%.

Women aged 41 or 42 years had significantly lower estimates (18.6% by conservative analysis and 27.8% by optimal analysis), which further declined to 6.6% and 11.3%, respectively, among those aged 43 years and older.

However, older women using donor eggs had better results; conservative and optimal estimates for women aged 41 to 42 years undergoing 3 cycles were 62.7% and 83.9%, whereas the corresponding rates for those aged 43 years and older were 64.1% and 79.6%, respectively, according to the article's appendix.

A subanalysis was conducted to examine the cumulative birth rates by cycle, showing that success rates did not improve after 3 cycles and that the attrition rate was approximately 30% for each consecutive cycle after the first.

The first cycle led to conservative and optimal birth rates of 31.5% and 26.4% of women discontinued therapy. For cycles 2, 3, 4, 5, 6, and 7, the conservative and optimal birth rates were 44.4% and 49.1%, 50.7% and 61.5%, 53.9% and 70.9%, 55.5% and 77.7%, 56.4% and 83.2%, and 56.8% and 87.0%, respectively, according to the appendix.

Live birth rates were lowest among women with diagnoses of diminished ovarian reserve or uterine-factor infertility, even after stratifying the analysis according to oocyte source and limiting the sample population to women younger than 40 years.

"In pregnancies conceived by means of assisted reproductive technology, uterine-factor infertility is also associated with adverse obstetrical outcomes, even with adjustment for age, which supports the principle that the uterine environment affects pregnancy outcomes," the authors write in the article.

After 3 cycles, conservative and optimal cumulative birth rate estimates among women diagnosed with diminished ovarian reserve or uterine-factor infertility ranged from 23.8% to 34.2% and from 43.3% to 54.4%, respectively. Rates were highest among those with polycystic ovary syndrome and other ovulation disorders (60.8% and 71.8%) or male-factor infertility (60.3% and 72.5%), according to the appendix.

Donor Eggs Help Tremendously

According to data in the appendix, for women with diminished ovarian reserve using donor eggs, the conservative and optimal cumulative birth rates were 65.9% and 83.7%, respectively, after 3 cycles and 70.6% and 97.6% after 7 cycles.

In addition, women with polycystic ovary syndrome using donor eggs experienced conservative and optimal birth rates of 56.5% and 79.9%, respectively; corresponding rates for those whose infertility was a result of male factors were not affected, at 44.6% for both.

Fresh donor eggs were more effective in achieving a live birth than the thawed version (range from 1 to 7 cycles, 49.3% to 99.1% vs 29.7% to 84.7%). No significant difference was found for those using their own eggs (32.0% to 82.6% vs 28.3% to 79.0%).

For both autologous and frozen oocytes, transferral of 2 embryos rather than 1 significantly improved success rates over the course of 3 cycles for women using their own eggs (49.1% to 76.7% vs 21.9% to 42.7%) or donor eggs (48.7% to 85.8% vs 61.1% to 92.3%), according to the appendix.

Transfer of 5- or 6-day-old blastocyst embryos was likewise associated with higher success rates compared with 2- or 3-day-old cleavage embryos. After 3 cycles, 52.4% to 80.7% of women whose embryos survived to blastocyst stage had given birth compared with 42.7% to 65.3% of those implanted with younger embryos.

For those using donor eggs, the corresponding rates ranged from 65.2% to 94.4% for blastocysts and 51.0% to 85.4% for cleavage embryos.

How to Improve Success Rates?

Although success rates are closer to what the authors report as "optimal" in countries such as Israel, where IVF is free, they note that discontinuation of treatment is not necessarily linked to financial burden.

"Previous studies in the United States and Europe have cited stress, lack of treatment success, and finances as the major reasons for discontinuation of treatment," they write, noting that drop-out rates are high even when IVF is covered by insurance (17% - 65%). In their study, 25% dropped out after an unsuccessful first cycle and 33% dropped out with subsequent cycles.

Dr. Shapiro concurred, saying, "There are many barriers to optimal outcomes in IVF. Where IVF is free, the primary barrier is clinic/lab competence. There are, unfortunately, too many variables in this regard to cover in [an interview]. Patient drop-out, even where coverage is assured, is a very common problem, and the main reason for it is the emotional burden of treatment."

The study was funded by the National Institutes of Health and the Society for Assisted Reproductive Technology. Full disclosure information is available on the journal's Web site.

N Engl J Med. 2012;366:2483-2491. Abstract

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