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As expected, researchers found costs were especially high for couples undergoing in vitro fertilization (IVF) - over $19,000, on average - and rose with each additional treatment cycle.
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That expense, he told Reuters Health, "has a big impact - they're taking out second mortgages on homes, they're borrowing from friends and family."
Smith and his colleagues interviewed 332 couples attending one of eight fertility clinics for their first evaluation and gave each a cost diary to record all treatment-related expenses. They then interviewed the couples three more times over the next year and a half about those expenses, including money spent on clinic visits and procedures, medications and miscellaneous items such as travel and parking.
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Expenses were higher for couples who took more time to get pregnant and underwent more treatment cycles, the researchers found.
However, there was no clear difference in out-of-pocket expenses based on whether couples reported having insurance coverage for fertility care, according to findings published in The Journal of Urology.
"Usually insurance companies will cover things like labs, the basic diagnostic testing," Smith said. "But the expensive items, like in vitro fertilization, that's much less well covered."
He said that is the case in California and most other states, but that a few - including Massachusetts and Illinois - require insurance companies to have more extensive coverage of fertility treatment.
According to the Society for Assisted Reproductive Technology, women received more than 150,000 cycles of IVF in 2011.
Dr. Vitaly Kushnir from the Center for Human Reproduction in New York said he would be "very cautious" about generalizing the new findings outside of the included clinics.
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He said the odds of becoming pregnant with each treatment option are also important to consider.
"It's not just how much does a given treatment cycle cost out of pocket, but how efficient or cost-effective are these treatments?" Kushnir said. "All of this comes down to the individual circumstances that the couple is facing."
Smith also said the choice of infertility treatment typically depends on the cause of the infertility. For example, if a man has a very low sperm count or a woman has blocked fallopian tubes, IVF is the only option that's likely to work.