Bemfola (follitropin alfa biosimilar) / Gedeon Richter - LARVOL DELTA

Randomized controlled trial to evaluate the impact of follicle priming on IVM outcomes in women with polycystic ovaries: CFA versus FSH-B. (PubMed, Hum Reprod) - P3 | "While follicle priming for IVM using one injection of CFA in subfertile patients with high AFC results in a trend towards lower oocyte retrieval rates compared to daily injections of FSH-B, the use of CFA in IVM cycles is safe, convenient, and as efficacious as priming with FSH-B."

Journal • Polycystic Ovary Syndrome

Biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART: a systematic review and meta-analysis. (PubMed, Hum Reprod) - "Clinicians should be informed that although biosimilars of follitropin alfa produce similar number of oocytes with the originator, pregnancy rates after a fresh transfer are likely to be lower. Future research should focus on optimizing the production and use of biosimilars of follitropin alfa, so that they lead to pregnancy rates comparable to the originator."

Clinical • Journal • Retrospective data • Review

Cumulative Pregnancy Rate With Lower and Higher Gonadotropin Dose During IVF Among Poor Responders (clinicaltrials.gov) - P=N/A | N=190 | Completed | Sponsor: Peter Kovacs MD | Recruiting ➔ Completed | N=700 ➔ 190

Enrollment change • Trial completion • Infertility • Sexual Disorders

Patient preferences on pen injectors for assisted reproductive technology: a discrete choice experiment in France. (PubMed, Expert Opin Drug Deliv) - "Estimation of the utilities showed statistically significant difference in favor of Gonal-f®/Pergoveris® (reference modalities) versus other pens, and the largest difference was with Rekovelle® [95% CI:-1,37;-0.85], and Bemfola® [95% CI:-2.25;-1,52]. This study show that respondent preferred pen that are ready to use, can be used multiple times, have dose injection confirmation, and display the dose with digits."

Journal • Infertility • Sexual Disorders

Clinical outcomes of three follitropin alfa preparations for ovarian stimulation using an oral micronized progesterone-primed protocol in an oocyte donation program. (PubMed, Front Endocrinol (Lausanne)) - "This large multicenter study aimed to evaluate clinical outcomes using three follitropin alfa preparations within a progestin-primed ovarian stimulation (PPOS) protocol, while identifying contributing factors to cycle success. No significant differences were observed in the cumulative live birth rate (CLBR) among oocytes obtained from stimulation with Bemfola (64.9%), Gonal-F (64.1%) and Ovaleap (66.1%), p= 0.385. This study demonstrated comparable clinical outcomes and CLBR between biosimilars and the reference product of follitropin alfa within PPOS protocols, hence they are interchangeable in a real-world patient setting."

Clinical • Clinical data • Journal • Retrospective data

Reply to Letter to Editor from Juan-Enrique Schwarze and colleagues - Critical appraisal on "Determining the cost-effectiveness of follitropin alfa biosimilar compared to follitropin alfa originator in women undergoing fertility treatment in France". (PubMed, Eur J Obstet Gynecol Reprod Biol X) - No abstract available

Cost effectiveness • HEOR • Journal

Pretreatment with luteal estradiol for programming antagonist cycles compared to no pretreatment in advanced age women stimulated with corifollitropin alfa: a non-inferiority randomized controlled trial. (PubMed, Hum Reprod) - P3 | "Programming antagonist cycles with luteal E2 pretreatment seems a useful tool in advanced age women to better schedule oocyte retrievals on working days. However, the potential benefit of the number of collected oocytes remains to be demonstrated in a larger population displaying the characteristics of decreased ovarian reserve encountered in Poseïdon classification."

Head-to-Head • Journal • Metastases • Gynecology

Determining the cost-effectiveness of follitropin alfa biosimilar compared to follitropin alfa originator in women undergoing fertility treatment in France. (PubMed, Eur J Obstet Gynecol Reprod Biol X) - "Sensitivity analysis showed that the originator's relative CLBR had the greatest impact on the model. This analysis demonstrates that the follitropin alfa biosimilar, Bemfola®, is a more cost-effective option for OS compared with the originator from a French healthcare payer perspective, in terms of cost per CLB."

Cost effectiveness • HEOR • Journal • Infertility • Sexual Disorders

Ovarian response and embryo ploidy following oral micronized progesterone-primed ovarian stimulation versus GnRH antagonist protocol. A prospective study with repeated ovarian stimulation cycles. (PubMed, Hum Reprod) - P=N/A | "In case of a freeze-all protocol, clinicians may safely consider oral micronized progesterone to control the LH surge and patients could benefit from the advantages of a medication of oral administration, with a potentially higher number of oocytes retrieved at a lower cost, without any compromise in embryo ploidy rates."

Journal

Serum progesterone is lower in ovarian stimulation with highly purified HMG compared to recombinant FSH owing to a different regulation of follicular steroidogenesis: a randomized controlled trial. (PubMed, Hum Reprod) - P4 | "Stimulation with hp-HMG may prevent progesterone elevation at the end of the follicular phase because of a different follicular steroidogenesis pathway, regardless of ovarian response. This should be considered, particularly in patients at risk of having high progesterone levels at the end of the follicular phase when a fresh embryo transfer is planned."

Journal • Infertility • Sexual Disorders

Reply to letter to the editor in response to 'A real-world study of ART in France (REOLA) comparing a biosimilar rFSH against the originator according to rFSH starting dose' by Montenegro S et al (JOGOH-D-23-00756). (PubMed, J Gynecol Obstet Hum Reprod) - No abstract available

Journal • Real-world • Real-world evidence

Androgen and inhibin B levels during ovarian stimulation before and after 8 weeks of low-dose hCG priming in women with low ovarian reserve. (PubMed, Hum Reprod) - P4 | "The results make us question the mechanism of action behind hCG priming prior to IVF. It is important to design a study with the puncture of small antral follicles before and immediately after priming to investigate the proposed hypothesis. Improved cycle outcomes, i.e. more retrieved oocytes, must be confirmed in a larger, preferably randomized study."

Journal

Eight weeks of androgen priming by daily low-dose hCG injections before ICSI treatment in women with low ovarian reserve. (PubMed, Hum Reprod) - P4 | "Long-term, low-dose rhCG administration may increase the number of oocytes retrieved during IVF/ICSI in women with low ovarian reserve, but more research is needed before firm conclusions can be drawn."

Journal

Determining the effects of follicle stimulating hormone (FSH) biosimilars on immunogenic and angiogenic responses of human granulosa lutein cells (Fertility 2023) - "hGLs were cultured for 5 days before stimulation -/+ 10ng/ml Gonal F (originator), Bemfola or Ovaleap (biosimilars) for 0, 8, 24,48-hours. r-hFSH preparations modulate the expression and secretion of cytokines and VEGF in hGLs, with potential distinct regulation of VEGF. This has implications for r-hFSHpreparation-specific regulation of granulosa cell functions."

Endometriosis • Gynecology • Women's Health • CXCL8 • IL6

A real-world study of ART in France (REOLA) comparing a biosimilar rFSH against the originator according to rFSH starting dose. (PubMed, J Gynecol Obstet Hum Reprod) - "Conclusions The REOLA study demonstrates that the cLBR with Bemfola® is very similar to Gonal-f® across all patient subpopulations. The cLBR is inversely related to the rFSH starting dose irrespective of the drug used, and the REOLA study provides reassurance of the clinical effectiveness of a biosimilar rFSH used in a real world setting."

Journal • Real-world evidence

E-Poster Abstract Station: W06 (ASRM 2022) - "OBJECTIVE: To assess clinical outcomes using different follitropin alfa preparations in the context of a progestin primed ovarian stimulation (PPOS) protocol and to identify confounding factors attributable to the success of the cycle MATERIALS AND Women accepted as oocyte donors and undergoing ovarian stimulation with 3 different follitropin alfa preparations Ovaleap® (Theramex Spain); n=3231, Bemfola® (Gedeon Richter Iberica); n=3542 or Gonal-F® (Merck SL) n=616...On the first FSH stimulation day, 10 mg acetate of medroxyprogesterone (MPA) was administered daily and then continued until GnRH agonist trigger (triptorelin)... As biosimilars have minor variations in sialylation from the originator, it is very reassuring that these small differences had no clinical impact when compared with the reference product. The different types of follitropin alfa are interchangeable in PPOS. IMPACT STATEMENT: No differences were found between different types of..."

Comparison of blastocyst euploidy rates following luteal versus follicular phase stimulation in a GnRH antagonist protocol: a prospective study with repeated ovarian stimulation cycles. (PubMed, Hum Reprod) - P=N/A | "The current study provides evidence that initiation of ovarian stimulation in the luteal phase in young potentially fertile women may result in a comparable number of oocytes and comparable blastocyst euploidy rates compared with follicular phase stimulation. This may imply that in case of a freeze-all protocol in young patients with good ovarian reserve, clinicians may safely consider initiation of ovarian stimulation during the luteal phase."

Journal • Infertility • Oncology

The effect of polymorphisms in FSHR gene on late follicular phase progesterone and estradiol serum levels in predicted normoresponders. (PubMed, Hum Reprod) - P=N/A | "Based on our results, FSHR SNPs rs6165, rs6166 and rs1394205 do not have any clinically significant impact neither on late follicular phase serum progesterone nor on estradiol levels in predicted normal responders. These findings add to the controversy in the literature regarding the impact of individual genetic susceptibility in response to OS in this population."

Journal

Cumulative Pregnancy Rate With Lower and Higher Gonadotropin Dose During IVF Among Poor Responders (clinicaltrials.gov) - P=N/A | N=700 | Recruiting | Sponsor: Peter Kovacs MD | Not yet recruiting ➔ Recruiting

Enrollment open • Infertility • Sexual Disorders

Overlapping biosimilar and originator follitropin alfa preparations: how much closer can they get? (PubMed, Drug Discov Today) - "Accordingly, the minor differences in 'ongoing pregnancy rate' and 'live birth' rate reported in a recent meta-analysis of biosimilars and Gonal-f® are probably driven by product-unrelated factors, notwithstanding the fact that of the four products under analysis, only Ovaleap® (from Theramex) and Bemfola® (from Gedeon Richter Plc) can unambiguously be considered to be biosimilars. The EU biosimilars model has proven successful, but given the distrust in biosimilars that is built on a biased foundation, the full promise of rFSH alfa biosimilars for reproductive medicine patients is unlikely to be fulfilled {AuQ: Edit OK?}. Teaser: {AuQ: Please provide the missing teaser.}."

Journal

Cumulative Pregnancy Rate With Lower and Higher Gonadotropin Dose During IVF Among Poor Responders (clinicaltrials.gov) - P=N/A; N=700; Not yet recruiting; Sponsor: Peter Kovacs MD

Clinical • New trial • Infertility • Sexual Disorders

Clinical Efficacy of Follitropin Alfa in GnRH-Antagonist Protocols: A Prospective Observational Phase IV Study on the Use of Biosimilar Follitropin Alfa r-hFSH in Assisted Reproductive Technology in a Routine Care Setting. (PubMed, J Reprod Infertil) - "Sixty-nine reports of ovarian hyperstimulation syndrome (7.0% of started cycles) were documented. COS with Bemfola in GnRH-antagonist IVF/ICSI protocols in a routine care setting led to an appropriate ovarian response allowing oocyte retrieval in 99.1% of initiated cases."

Clinical • Journal • Observational data • P4 data • Gynecology

The effect of polymorphisms in FSHR and FSHB genes on ovarian response: a prospective multicenter multinational study in Europe and Asia. (PubMed, Hum Reprod) - P=N/A | "A.R.N., B.A.M., C.S., J.M., L.H.L., P.Q.M.M., H.T., and S.G. report no conflict of interests. NCT03007043."

Clinical • Journal • FSHB

A large observational data study supporting the PROsPeR score classification in poor ovarian responders according to live birth outcome. (PubMed, Hum Reprod) - "C.A., J.P., G.P. and R.W. declare no conflict of interest. N/A."

Clinical • Journal • Observational data • Infertility • Sexual Disorders

The pharmacoeconomic impact of follitropin alpha biosimilars in IVF therapy in Europe: a report of the literature. (PubMed, Expert Rev Pharmacoecon Outcomes Res) - "In assisted reproductive treatments different gonadotropin biosimilars are being produced.Areas covered: For this reason, we performed a review of the literature on follitropin alfa Gonal-F biosimilar, Ovaleap and Bemfola, to assess their cost efficacy in national health system. In particular, they had only slight impact on cost reduction of recombinant follitropin alfa products in Europe.Expert opinion: considering cost-effective analysis, Gonal-F remains the first choice for national health systems. However, well-designed powered methods are strongly needed to assess biosimilars cost-effectiveness."

HEOR • Journal