REVIEWS AND COMMENTARY on recent literature in reproductive medicine and biology
The staff of THE REPRODUCTIVE TIMES here offers commentaries on recently published articles, primarily chosen for educational values—in the positive but also in the negative—for clinical purposes, and for their potential translational values to clinical medicine when addressing basic science in reproductive medicine and biology.
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Does using embryos from frozen donor eggs in fresh or in frozen-thawed embryo transfers make a difference?
A Research Letter in Fertility and Sterility attracted our attention: investigators pursued a study that was interesting in principle, asking whether it makes any difference whether embryos produced from frozen donor eggs after warming and fertilization should be—if possible—transferred fresh or could be frozen for later thaw and transfer. They attempted the answer through a sibling oocyte study and reported that there was basically no difference in cycle outcomes. In other words, there was no reason to be concerned about double cryopreservations (1).
But for several reasons we were not very happy with the peer review of this paper and those reasons first and foremost involved patient selection. It was not a lack of information on the oocyte donors (here the study population) because they were in principle well-defined with mean age of 25.5 years and mean BMI of 23.0 kg/m2. Their mean AMH level of 5.9 ng/mL and mean antral follicle count of 28.3, however, told a different story: Those values, of course, were anything but “normal” for an average group of egg donors.
Both of these values defined the investigated egg donor population as highly selected for unusually good functional ovarian reserve. They, indeed, in a majority must have been PCOS patients. Claims made by the authors of this research letter, therefore, do not apply to average egg donors who usually have lower functional ovarian reserve. The second reason for our unhappiness with the peer review of this Research Letter also relates to number of eggs retrieved from an oocyte donor because what ultimately defines the “value” of an egg donor is not the pregnancy/live birth rate achieved from a first embryo transferred using her eggs, but the cumulative pregnancy/live birth rate the donor cycle produces.
A single cycle sibling oocyte study, therefore, can really not offer an answer to the question the authors attempted to answer. A donor cycle’s first two oocytes chosen for this sibling study may be the best of the cycles’ total oocyte cohort. Results of remaining oocytes may be very different since better oocytes freeze and thaw better than poorer oocytes.
Finally, there is one more rather indisputable reason why this brief study cannot be taken seriously: every time we freeze either oocytes or embryos, we automatically lose cumulative pregnancy and live birth chances because at every thaw some eggs or embryos will not make it. The basic concept of this study, therefore, simply does not make sense as it is presented: just another example of deteriorating peer review in our specialty journals.
Reference
1. Barrison et al., Fertil Steril 2024;122(3): 536-537
Do co-transfers of poor embryos impact the results of good embryos?
Whether co-transferred embryos impact each other’s chances of implantation has been a question for decades, with studies offering different results. Considering the large variety of possible combinations of embryos, this should not surprise. Now investigators from China contributed another answer in a typical Chinese study of huge cycle numbers (n=11,738).
All cycles involved vitrified warmed blastocyst-stage transfers (between 2015 and 2022) and basically underwent single good-quality embryo transfer (n=9,338) or a double embryo transfer in which a good- quality blast was combined with a poor-quality embryo (2-ET, n=2,400).
Unsurprisingly, the live birth rate was significantly higher in the 2-ET group (65.6% vs 56.3%; P<0.001). Multivariable logistic regression demonstrated that 2-ET was an independent predictor of live birth rate (OR 1.55, 95%CI 1.41 to 1.71; P<0.001). Moreover, while a higher twinning rate was, of course, expected with 2-ET, the degree of difference was astonishing (1.8% vs 41.4%, P<0.001) (1).
While it appears safe to stop worrying about combining poorer with better embryos, the study raises serious additional questions regarding its credibility: First, to achieve in a general population of this size a 56.3% live birth rate either means an unbelievably good IVF program or—we, of course, do not wish to accuse our Chinese colleagues of any willful wrongdoing—incorrect outcome data presentation.
That 2-ET would produce a ca. 10% improvement in life birth rate to 65.5% would be within expected range. But a ca. 40% increase in twinning rate with only a ca. 10% improvement in live birth rate is again highly suspicious. It also raises questions about how the authors defined good- and poor-quality embryos. Simply based on the numbers it is, moreover, obvious that this was not a prospectively randomized study, but that good-prognosis patient usually received a single embryo, while poorer prognosis patients received a 2-ET. If confirmed, the study, therefore, also may suggest that the program may not very well differentiate between good- and poor-prognosis patients and between good and poor embryo quality. And if the program has these difficulties, how it would generate above noted superb live birth rates is difficult to understand.
We, therefore, have serious questions about the reported outcomes in this publication and wonder whether the journal’s editors requested submission of primary materials to the editorial office before acceptance of this paper. If not, one must ask, why not?
Reference
1. He et al., Reprod Biomed Online 2024;49(3):104104