Corifollitropin alfa for poor responders patients, a prospective randomized study

Abstract

Background: Poor ovarian response remains one of the biggest challenges for reproductive endocrinologists. The introduction of corifollitropin alpha (CFA) offered an alternative option to other gonadotropins for its longer halflife, its more rapid achievement of the threshold and higher FSH levels. We compared two different protocols with CFA, a long agonist and a short antagonist, and a no-CFA protocol. Methods: Patients enrolled fulfilled at least two of the followings: AFC < 5, AMH < 1,1 ng/ml, less than three oocytes in a previous cycle, age > 40 years. Ovarian stimulation with an antagonist protocol was performed either with 300 UI rFSH and 150 UI rLH or 300UI HMG. In the long agonist group, after pituitary suppression with triptorelin, CFA was given the 1-2th day of cycle and 300 UI rFSH and 150 UI rLH the 5th day. In the short antagonist group CFA was given the 1-2th day of cycle and 300 UI rFSH and 150 UI rLH the 5th day. The primary objective was the effect on the number of oocytes and MII oocytes. Secondary objective were pregnancy rates, ongoing pregnancies and ongoing pregnancies per intention to treat. Results: The use of CFA resulted in a shorter lenght of stimulation and a lower number of suspended treatments. Both the CFA protocols were significantly different from the no-CFA group in the number of retrieved oocytes (p < 0,05), with a non-significant difference in favour of the long agonist protocol. Both CFA groups yielded higher pregnancy rates, especially the long protocol, due to the higher number of oocytes retrieved (p < 0,05), as implantation rates did not differ. The cumulative pregnancy rate was also different, due to the higher number of cryopreserved blastocysts (p < 0,02). Conclusions: The long agonist protocol with the addition of rFSH and rLH showed the best results in all the parameters. A short antagonist protocol with CFA was less effective, but not significantly, although provided better results compared to the no-CFA group. We suggest that a long agonist protocol with CFA and recombinant gonadotropins might be a valuable option for poor responders. Trial registration: The study was approved by the local Ethics Committee (EudraCT2015-002817-31).

Corifollitropin Alfa Compared to Daily Recombinant FSH in in Vitro Fertilization Programmes: A Meta-Analysis of Randomized-Controlled Trials

“…The leave-one-out sensitivity analysis, conducted by serially excluding each study, confirmed the pooled results for almost all the outcomes, with the two following exceptions. When excluding the study by Fusi et al [24] we obtained a significantly higher cycle cancellation rate in the CFA group (OR 1.39, 95% CI [1.06, 1.81], p = 0.02; 7 RCTs, n = 4285; no heterogeneity: I 2 = 0%, p = 0.53). Fi-…”

“…Previous meta-analyses have been published with the aim to compare the ovarian stimulation with CFA and daily rFSH [25][26][27][28]. With respect to the latest recently published meta-analysis [28], the strengths of the present study comprise that our data updated the results by including four additional studies [17,21,23,24] and 640 more patients. More to the point, the present meta-analysis also combined the data regarding five outcomes previously not examined by Cozzolino and colleagues (2019) (duration of stimulation, cancellation rate, fertilization rate, implantation rate and miscarriage rate).…”

“…Of the remaining 14 studies, 2 were excluded after a full text evaluation. A total of 12 studies were included in the present meta-analysis [13][14][15][16][17][18][19][20][21][22][23][24]. The publication years ranged from 2004 to date and the characteristics of the included studies are summarized in Table 1 (Ref.…”

“…The publication years ranged from 2004 to date and the characteristics of the included studies are summarized in Table 1 (Ref. [13][14][15][16][17][18][19][20][21][22][23][24]).…”

“…Selection bias in the included studies was "unclear" considering that not all the trials reported adequate random sequence generation and detailed methods of allocation concealment. All the studies are blinded with "low" risk of performance with the exception of Devroey et al [13] Corifollitropin alfa dose-finding [14], Requena et al [17], Drakopoulos et al [20], Cruz et al [21], Sorouri et al [23] and Fusi et al [24]. No studies were assessor blinded and for this reason they were judged to be at "unclear" risk of detection bias, while regarding the attritition bias not all the studies reported complete outcome data with the exception of Devroey et al [15], Boonstanfar et al [19] and Vuong et al [22].…”