Federica Faustini, Danilo Cimadomo, Filippo Maria Ubaldi, M.D., Laura Rienzi
Fertility and Sterility Published: May 08
Promoting patient self-care is essential during infertility treatment. In assisted reproductive technology (ART), self- care includes managing stress, adopting a healthy lifestyle, and fulfilling each couple’s reproductive potential. Two to 6 out of 10 couples discontinue their treatment before achieving a healthy live birth (1), a figure largely dependent on reproductive history and maternal age. Indeed, treatment discontinuation is most probably the main reason why many infertile patients/couples do not completely exploit their reproductive potential. Nonetheless, this issue is still largely overlooked, perhaps because of ART professionals’ fear of being perceived as they are pushing patients into mul- tiple attempts. Nevertheless, clear information about multi- cycle rather than single cycle expected success rates, along with supportive counseling after a failure, are key to maxi- mize patients’/couples’ chance to conceive and critical from a self-care perspective.
Adopting a cycle-by-cycle perspective means planning with the patients/couple just one attempt and leaving the decision-making process about whether to undergo another cycle or not only after a failure. A multicycle approach, instead, entails admitting the likelihood of failures and dis- cussing the benefits of additional attempts upfront, antici- pating the decision-making process, and preparing the patients/couple for this scenario. Clearly, this counseling strategy should encompass the anticipation of all possible adverse outcomes throughout the journey, e.g., no response to ovarian stimulation, no oocyte available for insemination, no embryo available for transfer, or adverse reproductive out- comes after a transfer. Being informed beforehand of these risks and of their prevalence is critical to facing them; like- wise, being aware of the chance of success after a failure is useful to keep trying. From a psychological perspective, the greater the couple’s expectations invested on their first attempt, the greater their disappointment in case of failure, and the higher the risk for treatment discontinuation. Harri- son et al. (2) recently suggested that planning ahead what the treatment challenges might be could help rebuild hope af- ter treatment failure. Conversely, making important decisions under stressful circumstances makes the couple prone to give up (3). A multicycle approach would, thus, help patients and physicians to realistically discuss expectations and formulate fully informed treatment plans in line with how much they value becoming parents. According to the study by Harrison et al. (2), more than half of the patients encourage this coun- seling approach. Although this finding is interesting, it is certainly not surprising. Longstanding psychological the- ories, in fact, explain this patient behavior in health care, such as the ‘‘Theory of planned behavior’’ and the ‘‘Health Belief Model.’’ The Theory of planned behavior claims that a
behavioral intention can be expressed only if the behavior in question is under volitional control, namely, if the person is free to decide to exert a behavior being aware of the oppor- tunities and the resources required to meet those opportu- nities (e.g., time, money, and skills). The Health Belief Model, instead, suggests that the likelihood that a person will accept adopting a certain behavior can be predicted based on his/her understanding of the threats of the disease and the effectiveness of the treatment under evaluation. Both these theories emphasize the importance of supporting patients by translating their will into actions, even when difficulties are encountered. The ‘‘if-then’’ is crucial in this process to (i) effectively balance challenges with solutions, (ii) protect in- tentions from unwanted influences, and (iii) reinforce inten- tions and convert them into behaviors.
Recently, Harrison et al. (4) investigated the best way to implement a multicycle strategy in ART. They examined health care professionals’ and patients’ perceptions of different treatment planning approaches to explore the acceptability of a practice shift toward multicycle planning. Their main finding was that a cycle-by-cycle treatment strat- egy is perceived as clinically and emotionally safe, but they might consider a multicycle planning approach based on 3 prerequisites: (i) forewarning and expectation management, (ii) cooperation between patients and clinics, and (iii) support through challenging experiences. The patients support that a ‘‘personalized treatment plan,’’ shaped to convey a realistic understanding of their true opportunities and challenges and entailing the reassurance of support, would help them carry over throughout their planned journey.
Therefore, a multicycle perspective is possible and desir- able, but its application is advisable based on each profes- sional’s ethics. Patients should not be persuaded into agreeing to multiple treatments or add-ons in case of negli- gible cumulative chance of success or when these options are not aligned with their values and needs. Conversely, young patients with reduced ovarian reserve or advanced maternal age patients with good ovarian reserve are the ones most probably benefiting from this strategy.
Across the decades, we have witnessed several shifts in ART that changed our perspective from a single procedure- based to a cumulative vision. Intrauterine insemination was the first practice to be envisioned from a multicycle perspec- tive. Then the improvement of cryopreservation protocols and embryo selection strategies favored a multiple single embryo transfer approach vs. the well-established double embryo transfer one, ultimately triggering the implementation of a cumulative perspective in the evaluation of success in ART and decreasing the prevalence of multiple pregnancies. Lately, technology has advanced, and it is supporting coun- seling through big data, real world evidence, and artificial in- telligence to objectify the true estimates of success and tailor them to each couple.
From a clinical perspective, when adjusting for maternal age, a history of multiple idiopathic failures and/or miscar- riages does not foresee lower reproductive potential across consecutive cycles. Namely, each cohort of recruited oocytes is unique and involves an independent chance to succeed.
Several reports up to date, in fact, support that the cumulative live birth rate almost doubles across 3 consecutive attempts in any given population of patients.
In a population of women with very poor prognosis willing to conceive with their own oocytes, the DuoStim strategy might be considered after careful counseling. Duo- Stim is an unconventional stimulation protocol that entails 2 stimulations back-to-back in the same ovarian cycle and 2 oocyte retrievals in <1 month. At our center, a group of 41.0 2.9 years old patients who retrieved 4.9 3.1 cumulus-oocyte complexes after a first pick-up achieved a cumulative live birth rate of 24.5% with DuoStim vs. 12.6% in a matched group who instead preferred the conven- tional cycle-by-cycle approach. The reason at the root of this difference was that all couples choosing DuoStim inevitably underwent 2 ovarian stimulations, whereas the treatment discontinuation rate was >90% after a failure in the latter group, even if the second treatment was granted the same discounted price in both study arms (5). The bottom line here is that also in a very poor prognosis population of pa- tients, whenever the chance of success is not negligible, 2 oocyte retrievals in a short timeframe are effective to attempt at fulfilling their reproductive potential. DuoStim is thus a strategy to shorten the time to this end, but if we can counsel the patients to keep trying oocyte or (if allowed) embryo accumulation strategies, just like multiple attempts after consecutive conventional stimulation cycles, it would be as effective as DuoStim itself. Two putative disadvantages of DuoStim, although, are that the patients will be limited in their possibility to choose a different in vitro fertilization center and/or, in a setting where multiple attempts are covered by the national health care system, they will end up with a lower number of residual treatments in case of a failure. These limitations must also be acknowledged to avoid that DuoStim, as any other multicycle planning work- flow could be perceived as a commercial strategy to keep in- treatment patients with a negligible chance of success or restrain them from changing centers.
In conclusion, we think that the future of in vitro fertiliza- tion is characterized by 2 perspectives that are not mutually exclusive: either improve/restore oocyte and embryo compe- tence, especially in advanced maternal age women, or make treatments more affordable and patient-centered to support the couples after a failure and help them fulfill their personal chance to deliver a healthy baby. Our question, therefore, is: should the regular implementation of a multicycle counseling strategy be the next relevant shift in perspective needed in ART?