Dataset Information

The Effect of Dose Adjustments in a Subsequent Cycle of Women With Suboptimal Response Following Conventional Ovarian Stimulation.

ABSTRACT: Several infertile patients, who may even represent around 40% of the infertile cohort, may respond "suboptimally" (4-9 oocytes retrieved) following IVF, despite being predicted as normal responders. The aim of our longitudinal study was to evaluate the ovarian response of suboptimal responders in terms of the number of oocytes retrieved, following their second IVF cycle, evaluating exclusively patients who had the same stimulation protocol and used the same or higher initial dose of the same type of gonadotropin compared to their previous failed IVF attempt. Overall, our analysis included 160 patients treated with a fixed antagonist protocol in their second cycle with the same [53 (33.1%)] or higher [107 (66.9%)] starting dose of rFSH. The number of oocytes retrieved was significantly higher in the second IVF cycle [6 (5-8) vs. 9 (6-12), p < 0.001]. According to our results, a dose increment of rFSH remained the only significant predictor of the number of oocytes retrieved in the subsequent IVF cycle (coefficient 0.02, p-value = 0.007) after conducting GEE multivariate regression, while adjusting for relevant confounders. A regression coefficient of 0.02 for the starting dose implies that an increase of 50 IU of the initial rFSH dose would lead to 1 more oocyte.

SUBMITTER: Drakopoulos P

PROVIDER: S-EPMC6064928 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Effect of Dose Adjustments in a Subsequent Cycle of Women With Suboptimal Response Following Conventional Ovarian Stimulation.

Drakopoulos Panagiotis P Santos-Ribeiro Samuel S Bosch Ernesto E Garcia-Velasco Juan J Blockeel Christophe C Romito Alessia A Tournaye Herman H Polyzos Nikolaos P NP

Frontiers in endocrinology 20180723

Several infertile patients, who may even represent around 40% of the infertile cohort, may respond "suboptimally" (4-9 oocytes retrieved) following IVF, despite being predicted as normal responders. The aim of our longitudinal study was to evaluate the ovarian response of suboptimal responders in terms of the number of oocytes retrieved, following their second IVF cycle, evaluating exclusively patients who had the same stimulation protocol and used the same or higher initial dose of the same typ ...[more]

PMID: 30083131

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Project description:A suggested explanation for the pituitary-suppressive effects of progestin-primed ovarian stimulation cycles (PPOS) is pituitary luteinizing hormone (LH) depletion with progestin exposure during the follicular phase. The GnRH agonist (GnRHa) trigger releases endogenous LH from the pituitary, and if the LH depletion theory is correct, the response to the agonist trigger would be dampened in PPOS cycles. In this study, we compared the performance of the GnRHa trigger after PPOS and GnRH antagonist ovarian stimulation cycles. All women who underwent ovarian stimulation with the GnRH antagonist or flexible PPOS (fPPOS) and received a GnRH agonist trigger were eligible for inclusion. Outcomes included number of metaphase-II (MII) oocytes retrieved per cycle, rates of empty follicle syndrome, maturation, fertilization, blastulation, and cumulative clinical pregnancy per stimulation cycle. During the screening period, there were 166 antagonists and 58 fPPOS cycles triggered with a GnRH agonist. Groups were matched for potential confounders using propensity score matching. Progestin-downregulated cycles had 19% high mature oocyte yield (median: 14 vs. 19 MII oocytes, P = 0.03). Cumulative ongoing pregnancy or live birth rates were estimated after matching for transferred embryo count, and rates were similar between GnRH antagonist and fPPOS group (57.0% vs. 62.1%, P = 0.68). However, the number of remaining blastocysts was higher in the fPPOS group (median: 5.0 vs. 6.0, P < 0.001). LH levels were higher in fPPOS cycles compared to GnRH antagonist cycles up to the trigger day (P < 0.001). After the GnRHa trigger, fPPOS cycles were associated with a steeper LH surge compared with antagonist cycles (P = 0.02). Higher endogenous gonadotropin levels through the stimulation period and an LH surge of higher magnitude following a GnRHa trigger suggest a milder pituitary suppression by fPPOS, which needs to be confirmed in larger samples. It appears that progestins do not deplete pituitary LH reserves and a GnRHa trigger is usable after PPOS in women with high ovarian reserve.

Project description:ObjectiveTo assess and compare the feasibility of progestin-primed ovarian stimulation (PPOS) protocol with mild stimulation protocol for advanced age women with diminished ovarian reserve (DOR) undergoing their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle.MethodsPatients aged ≥35 years and DOR undergoing their first IVF/ICSI cycle were enrolled in this retrospective cohort study: 139 and 600 patients underwent the PPOS and mild stimulation protocols, respectively. The primary outcomes were cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR). The secondary outcomes were the number of oocytes retrieved and top-quality embryos.ResultsThere was nearly no significant difference of baseline characteristics between the two groups. Although a greater amount of total gonadotropin (1906.61 ± 631.04 IU vs. 997.72 ± 705.73 IU, P<0.001) and longer duration of stimulation (9 (10-7) vs. 6 (8-4), P<0.001) were observed in the PPOS group, the number of retrieved oocytes (3 (6-2) vs. 2 (4-1), P<0.001) and top-quality embryos (1 (2-0) vs. 1 (2-0), P=0.038) was greater in the PPOS group than the mild stimulation group. Meanwhile, the incidence of premature luteinizing hormone (LH) surge rate was significantly lower in the PPOS group (0.7% vs.8.3%, P=0.001) than the mild stimulation group. However, there was no significant difference in conservative CCPR, conservative CLBR, optimistic CCPR, and optimistic CLBR between the two groups (all P>0.05). A multivariate logistic regression model showed significant positive effects of the number of retrieved oocytes and number of top-quality embryos on conservative CCPR (OR=1.236, 95%CI: 1.048-1.456, P=0.012, OR=2.313, 95%CI: 1.676-3.194, P<0.001) and conservative CLBR (OR=1.250, 95%CI: 1.036-1.508, P=0.020, OR=2.634, 95%CI: 1.799-3.857, P<0.001) respectively, while significant negative effects of age were identified for conservative CCPR (OR=0.805, 95%CI: 0.739-0.877, P<0.001) and conservative CLBR (OR=0.797, 95%CI: 0.723-0.879, P<0.001).ConclusionThe PPOS protocol is an effective alternative to the mild stimulation protocol for advanced age patients with DOR, as it provides comparable reproductive outcomes and better control of premature LH surge. Further, more oocytes and top-quality embryos were obtained in the PPOS group, which had a positive association with conservative CCPR and CLBR.

Project description:BackgroundTo compare the efficacy and safety of follitropin delta in its individualized fixed-dose regimen with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. METHODS: This was a subgroup analysis of the randomized, multi-center, assessor-blind, non-inferiority trial (GRAPE) including 759 Chinese women (aged 20-40 years) recruited in 16 reproductive medicine clinics in China. Women were randomized in a 1:1 ratio to be treated with either follitropin delta dose based on anti-Müllerian hormone (AMH) and body weight or conventional dosing with follitropin alfa following a gonadotropin-releasing hormone (GnRH) antagonist protocol. The primary outcome was ongoing pregnancy rate assessed 10-11 weeks after embryo transfer in the fresh cycle (non-inferiority margin -10.0%).Results378 in the follitropin delta group and 381 in the follitropin alfa group were randomized and exposed. Non-inferiority was confirmed with respect to ongoing pregnancy with rates of 31.0% vs. 25.7% for follitropin delta compared to follitropin alfa, estimated mean difference of 5.1% (95% confidence interval (CI) -1.3% to 11.5%). The clinical pregnancy rate (35.4% vs. 31.5%, P = 0.239) and live birth rate (31.0% vs. 25.5%, P = 0.101) were comparable between the follitropin delta group and the follitropin alfa group. Overall, the individualized follitropin delta treatment resulted in fewer oocytes retrieved compared to follitropin alfa treatment (10.3 ± 6.2 vs. 12.5 ± 7.5, P < 0.001), which was mainly due to fewer oocytes (10.5 ± 6.4 vs. 13.9 ± 7.8) in women with AMH ≥ 15 pmol/L. Accordingly there was a lower incidence of early ovarian hyper-stimulation syndrome (OHSS) and/or preventive interventions (6.1% vs. 11.0%, P = 0.013). A daily follitropin delta dose of 10.2 µg (95% CI: 9.3-11.2 µg) was estimated to provide the same number of oocytes retrieved as a starting dose of 150 IU/d of follitropin alfa.ConclusionFollitropin delta in its individualized fixed-dose regimen showed similar efficacy and improved safety compared with follitropin alfa in a conventional adjustable dosing regimen in Chinese women.Clinical trial registration numberNCT03296527.

Dataset Information

The Effect of Dose Adjustments in a Subsequent Cycle of Women With Suboptimal Response Following Conventional Ovarian Stimulation.

Publications

The Effect of Dose Adjustments in a Subsequent Cycle of Women With Suboptimal Response Following Conventional Ovarian Stimulation.

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