Infertile women with polycystic ovary syndrome (PCOS) seemed to have a higher rate of live birth after undergoing in vitro fertilization (IVF) with frozen embryos compared with fresh embryos, a small study from China found.
Overall, nearly half (49.3%) the women with frozen embryo transfer had a live birth compared with 42% of women with fresh embryo transfer (relative risk 1.17, 95% CI 1.05 to 1.31, P=0.004). One potential explanation for this could be lower rates of pregnancy loss, as nearly a third of women in the fresh embryo group experienced a pregnancy loss compared to only 22.0% of the frozen-embryo group (RR 0.67, 95% CI 0.54 to 0.83, P<0.001), reported Zi-Jiang Chen, MD, of Shandong University in China, and colleagues.
Not only was the frequency of live birth after the first transfer higher, but frozen embryo transfer was associated with a significantly lower frequency of pregnancy loss and ovarian hyperstimulation syndrome, a potentially life-threatening medical condition affecting women taking fertility medication), they wrote in the New England Journal of Medicine.
However, compared with fresh embryo transfer, frozen embryo transfer was also linked with a higher rate of preeclampsia, they noted.
The frozen embryo versus fresh embryo debate has been long and ongoing among the IVF community, with certain recent evidence in favor of frozen embryo transfer. But this may be especially important for women with PCOS, the authors explained, because this population is particularly at risk for ovarian hyperstimulation syndrome (OHSS) and later pregnancy complications.
In an email to MedPage Today, Kaylen Silverberg, MD, of Ovation Fertility in Los Angeles, a national fertility service provider, said this confirms many of the findings about patients with PCOS that he has observed.
"Patients with PCOS are at high risk of ovarian hyperstimulation syndrome following IVF due, primarily, to their typically vigorous response to gonadotropin induced ovarian stimulation," said Silverberg, who was not involved with the research. "When embryos are frozen and the transfer is delayed until a subsequent cycle, the ovaries have a chance to recover. In addition, as no gonadotropin stimulation is required for frozen embryo transfers, embryos are transferred into a more physiologic uterine environment, there is essentially no risk of OHSS, and higher pregnancy rates result as well."
The researchers examined infertile women with PCOS undergoing their first IVF cycle. All the women were between ages of 20 and 34, and weighed at least 40 kg (about 88 lbs).
They randomized 762 patients to receive fresh embryo transfer and 726 patients to embryo cryopreservation, followed by frozen embryo transfer. Transfers occurred after 3 days of embryo development, and up to two embryos were transferred.
"This protocol potentially offers immediate benefits to women with PCOS, so practitioners should consider freezing all embryos for these patients," said co-author Richard Legro, MD, of Penn State College of Medicine in Hershey, in a statement.
The authors reported that the rates of OHSS were significantly higher among women with PCOS in the fresh group versus the frozen group (1.3% versus 7.1%, RR 0.19, P<0.001).
The preeclampsia rate among the frozen-embryo group was 4.4% compared with only 1.4% in the fresh-embryo group (RR 3.12, 95% CI 1.26 to 7.03, P=0.009). The authors said that this was consistent with prior observational studies, where frozen embryo transfers were associated with a higher risk of hypertensive disorders.
There were no significant differences in other pregnancy rates -- biochemical pregnancy, clinical pregnancy, ongoing pregnancy, ectopic pregnancy -- other pregnancy complications, neonatal complications, or congenital anomalies. The frozen embryo group had two stillbirths and five neonatal deaths, while the fresh embryo group had none.
But just because frozen embryo transfer was associated with positive outcomes when compared with fresh embryos, it does not mean there are no downsides to this procedure, pointed out Christos Coutifaris, MD, of University of Pennsylvania in Philadelphia, in an accompanying editorial. He argued that the many costs of frozen embryo transfer may be potential drawbacks.
"[There are] higher incremental financial costs (by a factor of 5 to 10) ... the emotional costs of deferring by 4 to 8 weeks the programmed frozen-embryo transfer, and the physical costs of additional treatments involving the administration of hormones, multiple injections and office visits," he wrote. "On the basis of current evidence, in women with a sufficient number of good quality embryos who are at low risk for implantation failure ... it may be reasonable to recommend fresh-embryo transfer as available."
Limitations to the study include that 10% of patients in each group may not have received the assigned treatment, which could have attenuated the between-group differences, as well as the fact that these results for women with PCOS may not be generalizable to other women undergoing IVF.
Also, the authors acknowledged that "the potential excess of neonatal death, owing primarily to prematurity, in the frozen-embryo group warrants attention."
They pointed out that the study was not designed to determine the mechanisms underlying their results, but "frozen-embryo transfer allows the ovary to recover from the ovarian stimulation and the exposed endometrial lining to shed, providing a fresh start for both."
The study was supported by the National Basic Research Program of China, the National Natural Science Foundation of China, and the Thousand Talents Program.