Follicle stimulating hormone biosimilar(Intas Biopharmaceuticals Ltd.)

This study aimed to characterize an interactive and clinically applicable population pharmacokinetic‐pharmacodynamic‐pharmacodynamic (PK‐PD‐PD) model describing follicle‐stimulating hormone (FSH)‐inhibin B‐oocyte relationship in women undergoing assisted reproduction with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The study was a prospective analysis of 25 healthy women undergoing IVF/ICSI using gonadotropin‐releasing hormone (GnRH) antagonist protocol. The developed model used the FSH PK profiles to predict both inhibin B (first PD end point) and oocyte retrieval (second PD end point). The modeling framework involved 2 stages. First, the FSH‐inhibin B model was developed by the simultaneous approach and applied to estimate the individual area under the inhibin B‐time curve (AUCInhb) at the end of stimulation cycles that varied in length in each woman. In the second stage, the estimated AUCInhb was introduced as a link covariate to predict oocyte retrieval and response category. The population FSH‐inhibin B model was described as 3 submodels; PK (exogenous), endogenous, and inhibin B PD models. Weight was the main determinant of both endogenous and exogenous FSH exposures. GnRH antagonist therapy was a significant time‐varying covariate when tested against the endogenous FSH production rate (P < .001). AUCInhb could be predicted with women's age and weight. Log‐transformed AUCInhb was a significant covariate when tested against oocyte retrieval (P < .001). Simulations concluded a target AUCInhb of 144‐303 ng·h/mL for optimal ovarian response. The GnRH antagonist was better started on day 7 of the cycle. Covariate‐based dosing suggests lower recombinant follicle‐stimulating hormone requirements in a thin and/or young population. An interactive web application “GonadGuide” was developed to facilitate the application in clinical practice.

To systematically review the efficacy of a combination of recombinant follicle‐stimulating hormone (rFSH) and recombinant luteinizing hormone (rLH) protocol versus human menopausal gonadotropin (hMG) protocol in controlled ovarian stimulation (COS).

PubMed, EMbase, The Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and WanFang Data were searched to collect studies published prior to January 2019 on the efficacy of rFSH combined with rLH versus hMG alone in COS. Two reviewers independently screened the literature, conducted the data extraction, and assessed the risk of bias for all selected studies. Then, Review Manager 5.3 software was used for the meta‐analysis.

There were 2767 patients from 9 studies. The results showed that among patients aged >30 years for IUI, the combination of rFSH and rLH was superior to hMG alone in clinical pregnancy rate per patient (relative risk [RR] = 1.47, 95% confidence interval [CI] 1.02 to 2.12) and endometrial thickness (mean difference [MD] = 0.34, 95% CI 0.04 to 0.64). In patients over 30 years old who received IVF, the results tended to favor the combination of rFSH and rLH in clinical pregnancy rate per patient (RR = 4.48, 95% CI 1.15 to 17.46) and live birth rate per started cycle (RR = 1.69, 95% CI 1.96 to 2.71). In patients less than 30 years old who received IVF, the combination of rFSH and rLH was superior to hMG in the number of retrieved oocytes (MD = 3.70, 95% CI 3.27 to 4.13) and inferior to hMG in number of high‐quality embryos (MD = –0.60, 95% CI –0.91 to –0.29).

The combination of rFSH and rLH may have better efficacy than hMG alone in COS. However, considering the limited sample size of the included studies, the current evidence is not definitive.