Document Type : Pictorial Review
Authors
1 Assisting NATURE, Unit of Human Reproduction and Genetics, Thessaloniki, Greece
2 University Hospital of Brussels, Dutch-speaking Free University of Brussels, Brussels, Belgium
3 Aristotle University of Thessaloniki, 3rd Department Ob Gyn, Thessaloniki, Greece
4 4Department of Reproductive Medicine, Hôpital Jean Verdier, Avenue du 14 Juillet, Bondy, France
Abstract
Keywords
Currently, the efficacy of
Although, there are certain laboratory parameters
that can be utilized to monitor the efficacy of a laboratory
team, such as fertilization rate, degeneration rate,
cleavage rate, blastulation rate, proportion of embryos
for freezing, unfortunately the embryological staff are
eventually solely judged by the pregnancy rates that their
lab is achieving. This is unfortunate, because many confounders
that intercede after their last involvement, such
as the type of embryo transfer catheter, the capacity of the
medical transferee, the quality of the endometrium, or the
quality of the luteal support, are factors that can be critical
for the efficiency of their work (
With the evolution of the Freeze-all strategy, a new problem is arising for evaluating the performance of an embryological team. Apart from the efficacy of the management of fresh gametes and embryos, we shall also take into consideration the efficacy of both freezing and thawing embryos. These are two extra procedures, which are both dependent on the expertise of the person who is performing these steps, therefore might potentially be at risk for mistakes. Moreover, the cryopreservation of all high responders and presumably good prognosis patients complicate the situation even more, as only poor or average responders are allowed to proceed with embryo transfer (ET), putting the probability of pregnancy with fresh embryo at risk in these poor prognosis patients.
Previously, the reports on pregnancy rates of an IVF unit were primarily based on the cases with fresh ET. Now with the frequent utilization of the freeze-all strategy there is a risks of reporting only poor prognosis patients, as all the good cases are postponed for thawed cycles.
The rationale for the freeze-all strategy and eventually segmentation of the IVF cycle has developed over the recent years and is based on two pathophysiological facts. The main one is the endometrial receptivity, which is definitely violated during ovarian stimulation due to the supra-physiological levels of the steroid hormones. Devroey et al. (
Ongoing implementation of the freeze-all strategy has indicated the need to establish a new representative index that may combine the success of both fresh and frozen cycles administered in the same woman, an index that may not be biased by the policy of an IVF center in favor of or against the freeze-all strategy (
The proposed COMFFETI index could be defined as a binomial variable [yes (1) or no (0)] reflecting the achievement of a pregnancy or not per individual (couple) at the end of each stimulated cycle; including fresh ET plus the thawed ET obtained by a single multifollicular ovarian stimulation cycle. This is a radically different index from the widely used index of pregnancy/delivery rate per transfer.
The basic difference lies in the fact that by the old way of reporting clinical or ongoing pregnancy per fresh ET reflects the potential of pregnancy achievement following this specific fresh ET (
Ηypothetical outcomes for hypothetical couples and potential reports in clinic A, which is fresh-cycle friendly
Patient | Fresh COCs | Produced embryos | Destiny | ET (n) | Cryo (n) | Fresh outcome | 1st frozen | 2nd frozen | DR/ET | COMFFETI |
---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 1D2 | Fresh ET | 1D2 | 0 | Neg | - | - | ||
2 | 9 | 6D3 | Fresh ET | 2D3 | 4D3 | Delivery | - | - | ||
3 | 17 | 6D5 | Fresh ET | 2D5 | 4D5 | Delivery | - | - | ||
4 | 12 | 5D5 | Fresh ET | 1D5 | 4D5 | Neg | Neg | Neg | ||
5 | 15 | 4D5 | Fresh ET | 1D5 | 3D5 | Neg | Neg | Delivery | ||
6 | 9 | 2D3 | Fresh ET | 2D3 | 2D3 | Neg | - | - | ||
7 | 11 | 6D3 | Fresh ET | 2D3 | 4D3 | Neg | Neg | Neg | ||
8 | 5 | 2D3 | Fresh ET | 2D3 | 0 | Neg | - | - | ||
9 | 10 | 5D5 | Fresh ET | 2D5 | 3D5 | Delivery | - | - | ||
10 | 10 | 6D3 | Fresh ET | 2D3 | 4D3 | Neg | Neg | Neg | ||
Overall | 30% (3/10) | 40% (4/10) | ||||||||
COCs; Cumulus oocytes, ET; Embryo transfer, Neg; Negative, and DR/ET; Delivery rate per fresh embryo transfer.
Hypothetical outcomes for the same hypothetical couples and potential reports in clinic B, which is freeze-ALL-friendly
Patient | Fresh COCs | Produced embryos | Destiny | ET (n) | Cryo (n) | Fresh outcome | 1st frozen | 2nd frozen | DR/ET | COMFFETI |
---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 1D2 | Fresh ET | 1D2 | 0 | Neg | - | - | ||
2 | 9 | 6D3 | Fresh ET | 2D3 | 4D3 | Delivery | - | - | ||
3 | 17 | 6D5 | FRALL | 0 | 6D5 | No ET | Delivery | - | ||
4 | 12 | 5D5 | Fresh ET 1D5 | 1D5 | 4D5 | Neg | Neg | Neg | ||
5 | 15 | 4D5 | FRALL | 0 | 4D5 | No ET | Neg | Delivery | ||
6 | 9 | 2D3 | FRALL | 0 | 2D3 | No ET | Delivery | - | ||
7 | 11 | 6D3 | Fresh ET 2D3 | 2D3 | 4D3 | Neg | Neg | Neg | ||
8 | 5 | 2D3 | Fresh ET 2D3 | 2D3 | 0 | Neg | - | - | ||
9 | 10 | 5D5 | FRALL | 0 | 5D5 | No ET | Delivery | - | ||
10 | 10 | 6D3 | FRALL | 0 | 6D3 | No ET | Delivery | - | ||
Overall | 20% (1/5) | 60% (6/10) | ||||||||
COCs; Cumulus oocytes, FRALL; Freeze all, ET; Embryo transfer, Neg; Negative, and DR/ET; Delivery rate per fresh embryotransfer.
The value of this new index could be demonstrated in case we examine two theoretical examples of different IVF centers, of which the first is in favor of fresh ET, while the second is practicing the freeze-all technique. Table 1 presents the final outcomes of 10 patients undergoing IVF treatment in an IVF center performing fresh ET. In case there were three deliveries achieved by the first ET with fresh embryos, the traditional index would have been 30%. Table 2 presents the same 10 patients undergoing IVF treatment and their final outcomes in a center taking the freeze-all approach. In case an IVF Unit has as mainstream policy to freeze embryos, the traditional delivery index would be only 20%. For instance case number 5 (due to high response) and case number 10 (due to high follicular progesterone) withheld the fresh transfer and took the freeze-all approach. Therefore, a superficial outcome of the two centers would indicate that centers favoring the fresh ET policy are more successful in achieving clinical pregnancies/deliveries.
Our own data support what was mentioned in the examples above about the COMFETI index. Based on the latest 50 cases of fresh embryo transfer cycles, the live birth rate has been 46% for the first embryo transfer, while the COMFFETI index has been 74% after two embryo transfers. Relatively, for the last 50 cases of the freeze-all strategy, the live birth rate was 58% for the first embryo transfer per case while the COMFFETI index was 82%. These results indicate the importance of using an index, which reflects the cumulative results of consecutive embryo transfers, especially in the freeze-all-friendly centers.
However, the consideration of pregnancies achieved “at the end of the day” according to COMFFETI index would radically change the situation. COMFFETI index would only have a slight increase from 20 to 30% in the first center, favoring fresh ETs, while in the second example, both cases 5 and 10 might have achieved a delivery with frozen embryos, and thus COMFFETI pregnancy rate could rise up to 60%, representing a totally different clinical outcome with regards to traditional index.
The additional great advantage that COMFFETI pregnancy rate provides is that it incorporates the implantation potential of all embryos produced from a single stimulated cycle. On the other hand, a drawback might be that COMFFETI rate is significantly related to the efficacy of cryopreservation techniques and the assumed increased success rates reported from the frozen cycles (
The basic endpoint of a successful IVF treatment cycle is giving a healthy baby to the mother (
The COMFFETI index in reproductive medical practice may be used to give the infertile patients a more subjective view about the realistic possibilities to have a successful IVF cycle from the beginning of the treatment. Moreover, reporting to organizations like European Society of Human Reproduction and Embryology (ESHRE) and Center for Disease Control would become increastingly objective by using the above index as a higher number of centers are moving towards the freeze-all policy, and therefore only poor cases or modest responders would be selected for fresh embryo transfers (