Management of Women With an Unexpected Low Ovarian Response to Gonadotropin

Abstract

POSEIDON groups 1 and 2 patients respond poorly (<4 oocytes retrieved) or sub-optimally (4–9 oocytes retrieved) to gonadotropin stimulation despite the presence of adequate ovarian parameters, which negatively affect their cumulative chances of delivering a baby using Assisted Reproductive Technology. A polygenic trait involving gonadotropins and/or their receptors seems to be the primary pathophysiology mechanism explaining this phenomenon. The clinical management is mainly focused on maximizing oocyte yield as to increase the likelihood of having at least one euploid embryo for transfer. Indices such as FORT (follicle output rate) and FOI (follicle-to-oocyte index) may be used to determine if the ovarian reserve was properly explored during a previous ovarian stimulation. Testing for the presence of common polymorphisms affecting gonadotropins and/or their receptors can also be considered to identify patients at risk of hypo-response. An individualized estimation of the minimum number of oocytes needed to obtain at least one euploid embryo can assist counseling and treatment planning. Among currently existing pharmacological interventions, use of recombinant FSH in preference over urinary gonadotropin preparations, FSH dosage increase, and use of rLH supplementation may be considered -alone or combined- for optimally managing POSEIDON's groups 1 and 2 patients. However, given the recent introduction of the POSEIDON criteria, there is still a lack of studies examining the role of interventions specifically to patients classified as groups 1 and 2, thus making it an area for open research.

COVID-19 and assisted reproductive technology services: repercussions for patients and proposal for individualized clinical management

“…Along these lines, the ART calculator -a clinical predictive model used to estimate the number of mature (metaphase II) oocytes needed to obtain at least one euploid embryo in couples undergoing ARTindicates that 13 (95% confidence interval [CI]: 11-16), 16 (95% CI: [13][14][15][16][17][18][19][20], and 19 (95% CI: 15-25) oocytes are needed for women aged 38, 39, and 40 years, respectively [10,11]. By contrast, only 5 (95% CI: 4-6) and 6 (95% CI: 5-7) oocytes are required for patients aged 33 and 34 years to have at least one euploid embryo [10,11].…”

“…The primary aim of the Poseidon criteria was to provide patient counselling and clinical guidance regarding interventions that could help these patients conceive in the shortest possible time. The most vulnerable Poseidon patients are those within groups 2 and 4, i.e., ageing patients 35 years or above, with (i) an unexpected suboptimal number of oocytes retrieved in a previous ART cycle despite a normal ovarian reserve (group 2), or (ii) low ovarian reserve in whom the number of oocytes resulting from ovarian stimulation is invariably low (group 4) [12,15,16]. The reason relates to the impact of maternal age and number of oocytes on the availability of euploid embryos, and thus, live birth.…”

“…Lastly, young patients with a diminished ovarian reserve and being at risk of premature ovarian insufficiency (i.e., Poseidon group 3) also represent a "timesensitive" category of women [15,26]. Due to the fact that Poseidon group 3 patients are younger than 35 years and, therefore, the oocyte/embryo euploidy rate is over 50%, the number of oocytes required to have at least one euploid embryo in these patients is lower than in older patients (e.g., 35 years and older) in whom the oocyte/ embryo euploidy rate is below 50% overall (e.g., Poseidon groups 2 and 4).…”

“…i. Poseidon group patients 2 could undergo ovarian stimulation and IVF for oocyte freezing or embryo freezing, as appropriate, as the ovarian reserve is still fair [15]; ii. Poseidon group 3 patients could undergo ovarian stimulation and ART for oocyte freezing or embryo freezing as the rate of oocyte and embryo aneuploidy is relatively low [26]; iii.…”

DuoStim – a reproducible strategy to obtain more oocytes and competent embryos in a short time-frame aimed at fertility preservation and IVF purposes. A systematic review

“…DuoStim, combining two consecutive stimulations spanning a 5-day interval, has been put forward as a valuable opportunity also for the management of poor-prognosis patients such as women with reduced ovarian reserve and/or advanced maternal age. The aim then is to maximize the number of oocytes retrieved in a single ovarian cycle, or to rescue patients in whom no oocytes were retrieved or competent embryos were not produced after conventional FPS (27)(28)(29)(30). For these thorny populations of patients, there is insufficient evidence to outline an ideal management since, regardless of the COS protocol adopted, consistently low live birth rates have been reported.…”