IVF Birth Rates Slightly Lower With Frozen Oocytes

Tara Haelle

August 11, 2015

Live birth rates for in vitro fertilization (IVF) cycles using frozen oocytes appear to be slightly lower than for those using fresh ones, according to a research letter published in the August 11 issue of JAMA.

"The reasons for lower live birth rates with use of cryopreserved oocytes remain to be established," write Vitaly A. Kushnir, MD, from the Center for Human Reproduction in New York City, and colleagues. "One possible explanation is less opportunity for proper embryo selection due to smaller starting numbers of oocytes, leading to fewer embryos available for transfer. Alternatively, oocyte quality may be negatively affected by cryopreservation and thawing."

However, the findings are based on anonymized aggregate outcomes, which means the researchers could not account for confounders, such as donor and recipient ages, infertility diagnosis, and embryo stage.

The data raise more questions than the authors can answer, Edmond Confino, MD, professor of obstetrics and gynecology at Northwestern Feinberg School of Medicine in Chicago, Illinois, told Medscape Medical News. "This article raises the fundamental question of what data should be applied to clinical medicine and which should be regarded as interesting or exciting," Dr Confino said. "It's an interesting study, and I think we have to pay attention to it, but the quality of the data does not make it applicable to clinical practice at this time."

The researchers analyzed 11,148 oocyte donation cycles included in the 2013 annual report of US IVF center outcomes published by the Society for Assisted Reproductive Technology. The report, containing data from 380 of 467 US-based fertility centers, represented 91.7% of all IVF cycles in 2013.

Of these, 20.0% (2227 cycles) used cryopreserved donor oocytes, 8.5% of which were cancelled after initiation compared with 11.7% of fresh oocyte cycles cancelled. Half (49.6%) of started recipient cycles with fresh eggs resulted in live birth compared with 43.2% of those with frozen eggs (6.4% difference; 95% confidence interval [CI], 4.1% - 8.7%; P < .001).

Live birth rates were slightly higher with embryo transfers, with 56.1% of fresh egg transfers and 47.1% of frozen egg transfers resulting in live birth (9.0% difference; 95% CI, 6.6% - 11.4%; P < .001). An average of 1.7 fresh-egg embryos and 1.6 frozen-egg embryos were transferred per cycle.

"Using eggs frozen by one center and thawed by another has potential negative impacts on success rates because of the use of different protocols," Tomer Singer, MD, a reproductive endocrinologist at Lenox Hill Hospital in New York City, told Medscape Medical News. "The commercial egg bank also has strict regulations on the shipment of finite numbers of eggs, which limits the selection process of which embryo to implant."

Less than 20% of the centers reviewed in the study are large academic centers with the experience and expertise to use this technique, "which skews the pregnancy rates downward," he said.

"I believe that undergoing egg freezing for social or medical reasons performed entirely in one academic center yields much higher pregnancy rates, eliminates the potentially problematic confounding factors, and may be the optimal choice for the patient," Dr Singer added.

Cryopreservation on the Rise

A notable finding in the study is the high number of egg donation cycles (20%) that used frozen eggs, according to Richard J. Paulson, MD, chief of the Division of Reproductive Endocrinology and Infertility at the University of Southern California Keck School of Medicine in Los Angeles. "That is a high number and indicates that the use of frozen eggs for egg donation is clearly on the rise," Dr Paulson told Medscape Medical News. "It also substantiates the idea that in the future, frozen donor eggs banks are going to be used more commonly."

The findings are not surprising, he said, adding that the difference in live birth rates was unlikely to be clinically significant. "We know that freezing technology has improved and that pregnancy rates are now similar, which is essentially the finding in this study," he said.

Dr Paulson also suggested that the wide range of potential confounders in the data set preclude conclusive findings.

"Comparison of pregnancy rates in the registry is problematic because you just cannot control for patient characteristics, clinic characteristics, etc, and patients self-select into the two treatment groups, so you just cannot conclude anything about differences between the two groups," Dr Paulson said. "With oocyte donation, the diagnosis and age of the recipient is not thought to play a role in the outcome, but of course there is no controlling for any other factor either."

The American Society for Reproductive Medicine declared egg freezing no longer experimental in January 2013 but also called for more data about safety and efficacy on the practice, which this letter attempted to provide, the authors write.

"I would advise reproductive endocrinologists and clinicians to interpret this data with caution, knowing that pregnancy rates with the use of frozen eggs have been shown to be equal, and in some institutions better, which is the reason [the American Society for Reproductive Medicine] had removed the experimental label on egg freezing," Dr Singer told Medscape Medical News. "Clinicians should not extrapolate from the data regarding live birth in donor frozen eggs when counseling young patients who wish to freeze their eggs for social reasons."

Three coauthors are co-owners of a number of already awarded and still pending US patents that are all unrelated to this topic. Two coauthors have received patent royalties from Fertility Nutraceuticals LLC. One coauthor also is a shareholder in Fertility Nutraceuticals LLC and owner of the Center for Human Reproduction. The other authors and commentators have disclosed no relevant financial relationships.

JAMA. 2015;314:623-624. Extract

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