Management Strategies for POSEIDON Groups 3 and 4

Abstract

In the POSEIDON classification, patients belonging to groups 3 and 4 share the same common feature of a poor ovarian reserve which independently of age renders them at high risk of a poor reproductive outcome. Overall, POSEIDON groups 1-4 constitute approximately 47% of patients attending assisted reproductive technology (ART) treatment. With the increasing delay in childbearing, POSEIDON group 4 seems to increase in numbers now in some centers constituting more than 50% of the total POSEIDON population, whereas group 3 patients constitute approximately 10%. Both POSEIDON groups 3 and 4 patients require special attention as regards pre-treatment strategy, ovarian stimulation, adjuvant treatment, and ovulation trigger strategy in order to optimize the probability of having at least one euploid blastocyst for transfer. Although more evidence is needed, recent advances seem to have increased the reproductive outcomes in the poor prognosis patient. The key to success is individualization in all steps of ART treatment. Herein, we review the recent evidence for the management of POSEIDON groups 3 and 4.

Keywords: ART calculator; Bologna criteria; POSEIDON criteria; blastocyst; controlled ovarian stimulation; poor ovarian response; pregnancy.

Figure 1

Online calculator to determine the minimum number of mature oocytes required to obtain at least one euploid blastocyst for transfer in infertile patients undergoing IVF/ICSI cycles. The figure shows how the online calculator can be used in an office-based setting. Pre-treatment, clinicians should input the patient age and the sperm source to be used for IVF/ICSI. If the option “Testicle” is marked, then the type of azoospermia should be also defined. The probability of success is set by the user and indicates the chance of having ≥1 euploid blastocyst when the predicted number of mature oocytes is achieved. Its complement is the risk, that is, the chance of having no (zero) euploid blastocysts when the predicted number of oocytes is achieved. Once the button “calculate” is pressed, a text box will pop-up on the right side of the screen, indicating the predicted minimum number of mature oocytes needed for obtaining at least one euploid blastocyst, with its 95% confidence interval (reprinted with permission of the author).

Figure 2

ART online calculator. The figure shows how the online calculator can be used post-treatment, i.e., when fewer than the predicted number of mature oocytes are obtained after one or more oocyte retrieval cycles. Clinicians should input the pre-treatment information and the actual number of mature oocytes collected or accumulated. The probability of success is set by the user; it reflects the chance that the estimation is correct given the number of oocytes input. Once the button “calculate” is pressed, a text box will pop-up on the right side of the screen, indicating the predicted probability of achieving ≥1 euploid blastocyst with the number of mature oocytes available (reprinted with permission of the author).

Figure 3

Best practice in POSEIDON groups 3 and 4. (A) Pre-treatment is rarely the first option in poor prognosis patients, but in case of unsuccessful ovarian stimulation, i.e., inadequate ovarian response, pre-treatment should be considered. The choice should rely on availability, clinical experience and patient preference. Stimulation protocol might start using GnRH antagonist co-treatment keeping in mind the possibility of converting to DuoStim to achieve the individualized oocyte number (according to the ART calculator). Otherwise a long GnRHa protocol should be considered first choice. (B) Ovarian stimulation strategy: First choice in Poseidon group 3 is the GnRH antagonist cycle with either 300 IU daily of rFSH alone or Corifollitropin alfa followed by either rFSH or hMG. In POSEIDON group 4 patients, rLH (75–150 IU daily) should be added from day one of stimulation unless the combination of Corifollitropin alfa and hMG was chosen. The GnRH antagonist cycle allows use of Duostim, unlike the long-agonist GnRH analog. (C) Ovulation trigger strategy: In the long GnRHa down-regulation protocol hCG is mandatory as ovulation trigger, whereas GnRHa is mandatory in the follicular phase stimulation of the DuoStim protocol. All trigger agents can be used in the luteal phase stimulation. In non-DuoStim GnRH antagonist cycles, the choice of trigger between GnRHa and hCG should rely on the embryo transfer strategy (fresh or frozen), patient characteristics (e.g., hypo-hypo) and clinical experience. In cases with a low FOI as determined on trigger day, clinicians should consider pre-treatment including short term estrogen therapy or OCP for synchronization of the follicles prior to stimulation, adjuvant LH activity during stimulation, or changing trigger strategy to either dual or double trigger. In case of an insufficient number of oocytes retrieved as determined by the ART calculator, the probability of transferring a euploid embryo should be discussed with the patient to counsel whether an immediate transfer or a new stimulation should be suggested.