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Study Authors: Repon C. Paul, Oisin Fitzgerald, et al.

Target Audience and Goal Statement: Obstetrician-gynecologists, pediatricians

The goal of this study was to assess cumulative live birth rates for women returning to in vitro fertilization (IVF), also known as assisted reproductive technology (ART) treatment, for a second child.

Question Addressed:

• What were the chances of having a second child via ART in women who had a first baby via fertility treatment?

Study Synopsis and Perspective:

Infertility affects about 15% of all couples, or over 180 million people worldwide. that has never occurred is known as primary infertility, whereas secondary infertility occurs with the failure to conceive after having achieved a previous conception. Infertility can affect both men and women.

ART, such as IVF, has revolutionized the treatment of infertility, with an estimated 7 million children conceived since the first ART-conceived baby was born in 1978. ART pregnancies in high-income countries represent .

The perspective of a complete cycle, which links all fresh and frozen embryo transfers to the associated ovarian stimulation, allows cycle-specific live birth rate and cumulative live birth rate to be calculated. The cycle-specific rates inform patients of their chances of a live birth from one course of ovarian stimulation followed by all embryo transfers, while the cumulative live birth rate informs patients of their chances of a live birth after a given number of repeated ovarian stimulation cycles.

Cumulative live birth rates per patient over successive "complete" ART cycles, which includes outcomes from fresh/cryopreserved embryo transfers following an ovarian stimulation cycle, are considered the preferred measure of IVF treatment success.

Prior studies have not addressed the facilitation of patient counseling and clinical decision-making on ART success rates for these patients. Therefore, Georgina Chambers, PhD, of the University of New South Wales in Sydney, Australia, and colleagues embarked on a population-based cohort study to identify factors associated with returning to ART treatment for a second child and to calculate the cycle-specific live birth rate and the cumulative live birth rate for up to six ART cycles for these women.

Women have a good chance of having a second child with the help of fertility treatment after the birth of their first child born this way, they reported in . This study was the first to report the chances of having a second ART-conceived child among women using their own eggs.

The researchers calculated that after having a first baby with the aid of ART, the chances of having a second baby were between 51% and 88% after six cycles of treatment. Estimates depended on the use of fresh or frozen embryos, and on assumptions made about the likely success rate for women who discontinued treatment.

The researchers analyzed data from the Australian and New Zealand Assisted Reproduction Database (ANZARD) for ART cycles performed at the 90 included clinics from January 2009 to December 2015. Complete registration was assumed, as in these countries must report all cycles to ANZARD as part of the licensing agreement. The study population included 35,290 women who had an ART-conceived infant, and received treatment from 2009 to 2013. Women were followed for a further 2 years to 2015, providing between 2 and 7 years of follow-up data, and live births up to October 2016 were included. The researchers excluded cycles that used donated oocytes or embryos, as well as any treatment for the purpose of long-term oocyte or embryo storage only.

"We explored two questions: what is a woman's chance of achieving a second live birth in a particular cycle of treatment if previous cycles have failed, for instance in cycle three if the first two cycles have failed; and what is the overall, or cumulative, chance of a woman achieving a live birth after a particular number of cycles, including all the previous cycles. For example, what is the overall chance of a woman having a baby after up to three cycles?" Chambers said in the press release.

Treatment characteristics of the cycle that resulted in the first live birth included number of previous complete cycles, number of oocytes collected, type of treatment (IVF or intracytoplasmic sperm injection), number and stage of embryo transfer, and type of embryo transfer (fresh or frozen). "A complete cycle was defined as all fresh and frozen embryo transfer cycles resulting from a single ovarian stimulation," the researchers wrote.

After six complete cycles, plus any surplus frozen embryos, the cumulative live birth rate for the 15,325 women (average age 36 years) who recommenced fertility treatment with a frozen embryo was 61% to 88%, compared with 51% to 70% for those who underwent a new ovarian stimulation cycle.

The live birth rate in the first complete cycle was 43.4% for those who used a frozen embryo from the previous treatment, and 31.3% for women who started a new ovarian stimulation cycle. Although cycle-specific live birth rates declined in successive cycles, cumulative live birth rates increased for all age groups up to six cycles.

Chances of a second ART baby decreased with age. "Factors that improved their chances of a successful second pregnancy included requiring only one cycle and a single embryo transfer to achieve a first live birth, and where infertility was caused by factors affecting the male partner," said Chambers in a .

After three cycles of treatment, the conservative and optimal cumulative live birth rates in women ages 40 to 44 who started with frozen embryos were 38% and 55%, respectively. Corresponding estimates among those who recommenced with a new stimulated cycle and fresh embryos were 20% and 25%, respectively.

"Frozen embryos remaining from a previous cycle originate from a biologically younger patient than those created in a new cycle," said co-author Christos Venetis, MD, also of the University of New South Wales, in the press release. "Frozen embryos also tend to indicate a better prognosis, since these women were able to produce multiple good quality embryos," he added.

Study limitations, Chambers and colleagues said, included that the research does not account for individual prognostic factors that may affect a woman's chance of IVF success, including the duration of infertility, body mass index, and ovarian reserve. In addition, since use of IVF is high in Australia and since it is included in universal healthcare coverage, the study's generalizability to other groups may be limited.

Source Reference: 2020; DOI: 10.1093/humrep/deaa030

Study Highlights and Explanation of Findings:

"This is the first time that the estimates for the chances of having a second baby using IVF have been calculated," Chambers told 麻豆传媒 via email. "This is important because most couples want more than one child. And those that had to use IVF to achieve their first baby are likely to need IVF again."

In this study, more than 15,000 women returned to IVF treatment for their second child. Women who were younger or nulliparous at the time of their first ART-conceived child were more likely to return, and were also more likely to have had a fresh embryo transfer.

Alan Penzias, MD, director of the Fellowship Program in Reproductive Endocrinology and Infertility at Harvard Medical School in Boston, who was not involved with the study, commented that it reflects a shift in thinking about treatment for infertility.

"In the early days of IVF when success rates were low, the focus was getting to 'the baby,'" he told 麻豆传媒. "Having a second child was rarely considered. Nowadays, we ask couples what they see as their ideal family size at the first visit, so understanding how likely a second child is after the first success becomes very relevant."

Penzias added that the study not only helps physicians quantify the chances of a second IVF success, but also allows them to understand what characteristics lead to that success. "Having this information can help physicians understand who to counsel to persist and who should be counseled to think about other alternatives," he said.

In the press release, co-author Devora Lieberman, MD, a fertility clinician at City Fertility in Sydney, agreed that these results can be used to counsel patients. The major caveat was that these were population estimates and that every couple is different.

"Our analysis does not take account of all individual factors that affect a woman's chance of ART success, including duration of infertility, and body mass index. Whether ART treatment should be commenced or continued should ultimately be a decision for the fertility clinician and patient, taking into account all medical and non-medical factors. But this study provides the range of results that could be expected," she said.

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