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According to a new, large population-based study in Australia, women who conceived their first child via assisted reproductive technology (ART) and returned for a second baby had better than even probability of getting pregnant again.

As shown in the online study in Human Reproduction, for women who started in vitro fertilization (IVF) for their second baby with fresh embryos, cumulative live birth rates were between 51% and 70%.

Analysis of the promising study was published in a recent article of MedPage Today – featuring commentary from Boston IVF reproductive endocrinologist Alan Penzias, MD – who was not involved in the study but lauded its potential to help physicians quantify the chances of a second IVF success and understand what characteristics lead to that success. 

In addition to the full article’s content – which is available below – we’ve added some additional commentary from Dr. Penzias here.

Q&A with Alan Penzias, MD

Q: To your knowledge, have other studies investigated live birth rates among women returning for assisted reproduction the second time? Why is it significant to understand this?

ALAN PENZIAS, MD
IVF success rates have been studied in a number of ways. Each method answers a different question. The simplest method is calculating success on a “per cycle” basis. The information is useful for comparing populations of different ages or other characteristics but it does not answer some important questions.

For example, a couple who ask how likely they are to have a baby when all is said and done. It also doesn’t distinguish between the odds of success in the first cycle of treatment vs the 3^rd such treatment.

Cumulative live birth rates are typically measured from the first cycle of over a series of treatments. The endpoint is a first baby. It can answer questions about how the odds of success change between cycles. However, since the endpoint is a first baby it doesn’t answer the question about the likelihood of having a second child.

The novelty of the current study is that it asks how likely it is to have a second IVF baby after having had a first child with IVF. The significance of the study is how it reflects a shift in thinking. In the early days of IVF when success rates were low the focus was getting to “the baby”. Having a second child was rarely considered. Nowadays, we ask couples what they see their ideal family size is at the first visit so understanding how likely a second child is after the first success becomes very relevant.

Q: What was noteworthy about this study's results? Did anything surprise you?

ALAN PENZIAS, MD
It would be logical to think that patients who have succeeded with IVF once have a good chance of succeeding again. The study provides a very useful tool to physicians who want to quantify those odds more precisely. Further, it helps us understand the characteristics that lead quickly to a second success and the variables that are less important or even negative prognostic factors. Having this information can help physicians understand who to counsel to persist and who should be counseled to think about other alternatives.

Q: Do you think these results are generalizable in a domestic, U.S. context?

ALAN PENZIAS, MD
A limitation that the authors point out is that their study doesn’t fully account for individual prognostic factors including duration of infertility, Body Mass Index and Ovarian Reserve.  Also, utilization of IVF services is higher per capita in Australia and New Zealand because it’s part of their national health coverage. In the USA, infertility services are covered by insurance in a relatively small number of states.  When counseling a US patient I’d cite those limitations but still say the relative differences have value.

Q: Does this research add anything unique to the field?

ALAN PENZIAS, MD
The research validates methodologies for examining cumulative IVF success rates that are gaining traction and gives us (researchers in the US) impetus to look at our own large databases and see if our findings are the same or differ. That benefits patients everywhere.

Q: What might explain higher success rates in frozen versus fresh embryos?

ALAN PENZIAS, MDWhile an embryo of any developmental stage and grade can be transferred fresh, not all embryos are freezable. The poorer quality embryos may stop dividing and never make it to a stage where they can be frozen. Further, in a fresh IVF cycle the focus is primarily on follicle size and development. In a frozen cycle the embryo stage and grade are already known and the focus in  on optimizing the uterine lining.

Q: Any clinical implications?

ALAN PENZIAS, MD
For those patients who want more than one child, there may be an advantage to having frozen embryos available from the first IVF cycle to use as frozen embryos for the second child.

Women Have a Good Chance of Secondary Pregnancy

Storing Frozen Embryos from 1^st IVF Treatment May Be an Advantage

by Amanda D'Ambrosio, Staff Writer, MedPage

www.medpagetoday.com / May 8, 2020

Women who conceived their first child via assisted reproductive technology (ART) and returned for a second baby had better than even probability of getting pregnant again, according to a large population-based study.

After six complete cycles, women who recommenced ART treatment with previously frozen embryos had a cumulative live birth rate of 61% to 88%, depending on assumptions made about the likelihood of success in women who dropped out of treatment, reported Georgina Chambers, PhD, of the University of New South Wales in Sydney, Australia, and colleagues.

As shown in the team's study online in Human Reproduction, for women who started in vitro fertilization (IVF) for their second baby with fresh embryos, cumulative live birth rates were between 51% and 70%.

Of more than 35,000 women in Australia and New Zealand who conceived a child via ART, 43% returned to treatment for a subsequent pregnancy, the researchers said.

"This is the first time that the estimates for the chances of having a second baby using IVF have been calculated," Chambers told MedPage Today 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."

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.

Women who conceived their first child via assisted reproductive technology (ART) and returned for a second baby had better than even probability of getting pregnant again, according to a large population-based study.

After six complete cycles, women who recommenced ART treatment with previously frozen embryos had a cumulative live birth rate of 61% to 88%, depending on assumptions made about the likelihood of success in women who dropped out of treatment, reported Georgina Chambers, PhD, of the University of New South Wales in Sydney, Australia, and colleagues.

As shown in the team's study online in Human Reproduction, for women who started in vitro fertilization (IVF) for their second baby with fresh embryos, cumulative live birth rates were between 51% and 70%.

Of more than 35,000 women in Australia and New Zealand who conceived a child via ART, 43% returned to treatment for a subsequent pregnancy, the researchers said.

"This is the first time that the estimates for the chances of having a second baby using IVF have been calculated," Chambers told MedPage Today 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."

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 MedPage Today. "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.

Around 15% of couples, or 180 million people worldwide, experience infertility, Chambers and colleagues wrote. The aim of their study was to identify factors associated with returning to ART treatment for a second child, and to calculate both cycle-specific and cumulative live birth rates.

The researchers looked at data from the Australian and New Zealand Assisted Reproduction Database for ART cycles performed from 2009 to 2015. The database includes all 90 fertility clinics in these two countries, which are required to report ART cycles for licensing agreements.

The study population included 35,290 women who had an ART-conceived infant, and received treatment from 2009 to 2013. Women were followed up for 2 to 7 years, and all live births up to 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.

The group adjusted for women's age, the cause of infertility at the second time of ART treatment, and the time between the first ART-conceived live birth and the second treatment, as well as the parity and characteristics of the first treatment.

More than 15,000 women returned to IVF treatment for their second child. Those who were nulliparous at the time of their first ART-conceived child and those who were younger were more likely to return, and were also more likely to have had a fresh embryo transfer, the researchers reported.

During the second ART treatment, women more likely to have a second live birth were younger, had frozen embryos stored from their first IVF treatment, had a shorter time between the birth of their first child and second treatment, and got pregnant in the first few cycles.

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.

Among women younger than 30, live birth rates were similar for those who started their second treatment with previously frozen or fresh embryos. Yet for older women, live birth rates were better for those who used frozen embryos.

Regarding the clinical implications, Penzias said: "For those patients who want more than one child, there may be an advantage to having frozen embryos available from the first IVF cycle to use as frozen embryos for the second child."

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.

Disclosures

The researchers reported that no funding was received to undertake the study.

Chambers reported being a paid employee of the University of New South Wales (UNSW) and director of the university's National Perinatal Epidemiology and Statistics Unit. The Fertility Society of Australia contracts UNSW to prepare the Australian and New Zealand Assisted Reproductive Technology Database (ANZARD) annual report series and benchmarking reports. Co-authors reported relationships with MSD, Merck, Serono, Beisins, and Ferring Pharmaceuticals.