HELSINKI – A freeze-all strategy in women of advanced maternal age who are undergoing in vitro fertilization appears to increase the likelihood of pregnancy, according to findings from two retrospective cohort studies.
In one matched cohort study comparing the outcomes of 1,636 freeze-all cycles and 1,636 fresh cycles, the ongoing pregnancy rates were 50% for freeze-all cycles and 44% for fresh cycles. After controlling for hormone levels, number of embryos transferred, diagnosis, age, and preimplantation genetic screening utilization, the investigators found that the difference was largely attributable to an effect in older women; the ongoing pregnancy rate was significantly higher in freeze-all cycles, compared with fresh cycles, among patients over age 35 years (46% vs. 33%; odds ratio, 1.6), Karen Hunter Cohn, PhD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
A benefit of frozen vs. fresh cycles also was seen among women with elevated progesterone levels prior to egg retrieval, and this was true regardless of age; the pregnancy rates for freeze-all vs. fresh cycles in those over age 35 years with progesterone levels over 1.3 ng/ml were 54% and 45%, respectively (OR, 1.4), and for those under age 35 with elevated progesterone, they were 44% and 30%, respectively (OR, 1.4), said Dr. Cohn, of Celmatix in New York.
However, a diagnosis of polycystic ovarian syndrome, endometriosis, tubal disease, or unexplained infertility had no significant impact on outcomes.
In another study comparing outcomes of 1,180 fresh embryo transfers and 517 frozen transfers after a freeze-all strategy in 1,469 women, the clinical pregnancy rates were higher for frozen transfers both in women under age 39 years (44.5% vs. 38.2%) and in those aged 39 years and older (34.9% vs. 22.7%), Sara Lopez, MD, reported during an abstract session.
Multivariate analysis showed a significantly positive effect of performing frozen transfers in both age groups, but the effect was greater in the older age group (OR, 1.60 vs. 1.39), said Dr. Lopez, of Clinica CIRH in Barcelona.
No difference was seen in miscarriage rates in either group, she noted.
Dr. Cohn’s study included patients from 12 fertility treatment centers in the United States who underwent IVF cycles from 2009 to 2015. Dr. Lopez and her colleagues studied women who underwent IVF between January 2014 and December 2015.
Both authors noted that IVF with frozen embryo transfer has become more common, and that freeze-all protocols in which all embryos are frozen and transferred in a later cycle have emerged to reduce the risk for ovarian hyperstimulation syndrome (OHSS), and to address concerns about endometrial receptivity in women undergoing controlled ovarian stimulation and/or experiencing a premature elevation of progesterone.
However, randomized controlled studies comparing the two approaches have focused only on good prognosis patients, and thus have not addressed which patients might benefit most from a freeze-all protocol, Dr. Cohn said.
Dr. Lopez further noted that “older IVF patients usually present with a diminished ovarian reserve and suboptimal oocyte quality.”
“These women are not normally at risk for ovarian hyperstimulation syndrome, so they usually have the best embryos transferred during a fresh cycle and are therefore exposed to embryo-endometrium asynchrony,” she explained, adding that since suboptimal embryo quality cannot be amended, efforts should be directed toward providing the best endometrial environment for embryo transfer.
Though both studies are limited by their retrospective design, the authors each concluded that a freeze-all strategy appears to be the best approach to achieving that environment in older women.
Eric A. Widra, MD, of Shady Grove Fertility in Washington, and one of Dr. Cohn’s coauthors, noted in a press statement that interest in a freeze-all approach is growing but is not used broadly.
“There are several reasons clinics do freeze-all cycles. These include patients at high risk for OHSS, patients having preimplantation genetic diagnosis prior to embryo transfer, and, importantly, those patients who have a premature rise in the concentration of progesterone hormone prior to egg retrieval. Several studies have shown that this rise in progesterone is associated with a lower pregnancy rate after fresh embryo transfer,” he said, concluding that while the evidence is intriguing, a prospective randomized study will be necessary to conclude whether a freeze-all strategy is effective for any group of patients.
Dr. Cohn is an employee of Celmatix. Dr. Widra and Dr. Lopez reported having no disclosures.