Corifollitropin alfa for ovarian stimulation in in vitro fertilization: a systematic review and meta-analysis of randomized controlled trials

Abstract

Objective: To evaluate the effectiveness of corifollitropin alfa in improving the success of IVF. Design: Systematic review and meta-analysis. Setting: Not applicable. Patient(s): Infertile women undergoing conventional IVF or intracytoplasmic sperm injection (ICSI). Intervention(s): Randomized controlled trials (RCTs) of infertile women undergoing a single IVF/ICSI cycle with either corifollitropin alfa or a conventional ovarian stimulation protocol based on daily injections. The review protocol was registered in PROSPERO before starting the data extraction (CRD42018088605). Main Outcome Measure(s): Primary outcomes were live birth rate and/or ongoing pregnancy rate. Clinical pregnancy rate, miscarriage rate, multiple pregnancies, number of oocytes and embryos obtained, cancellation rate, and rate of ovarian hyperstimulation syndrome and ectopic pregnancy were considered as secondary outcomes. Result(s): Eight randomized controlled trials were included; 2,345 women were assigned to the intervention group and 1,995 to the control group. The analysis of 4,340 IVF cycles did not reveal any difference in live birth rate and/or ongoing pregnancy rate between groups (risk ratio [RR], 0.92; 95% confidence interval [CI], 0.80-1.05). Similarly, no difference was found in clinical pregnancy rate (RR, 0.96; 95% CI, 0.88-1.05; I 2 ¼ 0%), miscarriage rate (RR, 0.94; 95% CI, 0.71-1.25; I 2 ¼ 0%), or multiple pregnancy rate (RR, 1.22; 95% CI, 0.99-1.50; I 2 ¼ 0%). Also, the rates of cycle cancellation, ovarian hyperstimulation syndrome, and ectopic pregnancy were similar in both groups. Sensitivity and subgroup analyses did not provide statistical changes to pooled results. Conclusion(s): Corifollitropin alfa seems to be an alternative for daily recombinant FSH injections in normal and poor responder patients undergoing ovarian stimulation in IVF/ICSI treatment cycles. (Fertil Steril Ò 2019;111:722-33. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

Corifollitropin-α is useful for low and normal responders, but what about hyperresponders?

“…The authors did not find any difference in the rates of live birth, overall pregnancy, clinical pregnancy, pregnancy wastage (miscarriage), multiple gestation, cycle cancelation, ovarian hyperstimulation syndrome (OHSS), or ectopic pregnancy (1). Therefore, the authors correctly concluded that corifollitropin-a is as effective as recombinant follicle-stimulating hormone (FSH) for IVF in normal or low responders (1). Furthermore, the number of the total retrieved oocytes, metaphase 2 (MII) oocytes, and generated embryos were statistically significantly higher in the patients treated with corifollitropin-a compared with the group receiving daily FSH injections (1).…”

“…Although after 40 years the practice of in vitro fertilization (IVF) has come of age, controlled ovarian stimulation for assisted reproductive technology (ART) continues to undergo changes to improve clinical outcomes and make the overall treatment experience less expensive and more comfortable, simple, and user-friendly. In this issue of Fertility and Sterility, Cozzolino et al (1) summarize randomized controlled trials (RCTs) with infertile women who underwent a single cycle of IVF with intracytoplasmic sperm injection (ICSI) cycle using either corifollitropin-a or a conventional ovarian stimulation protocol based on daily injections (1). The authors correctly explain that the use of daily injections for infertility treatment may augment the patients' anxiety due to the possibility of unintentional mistakes.…”

“…The authors have included eight RCTs for a total of 2,345 women who received corifollitropin-a compared with 1,995 control patients who received daily gonadotropin injections as ovarian stimulation for IVF or ICSI (1). The authors did not find any difference in the rates of live birth, overall pregnancy, clinical pregnancy, pregnancy wastage (miscarriage), multiple gestation, cycle cancelation, ovarian hyperstimulation syndrome (OHSS), or ectopic pregnancy (1). Therefore, the authors correctly concluded that corifollitropin-a is as effective as recombinant follicle-stimulating hormone (FSH) for IVF in normal or low responders (1).…”

“…However, the included RCTs were only of low or normal responders (1). All the protocols used gonadotropinreleasing hormone (GnRH) antagonists, not the long GnRH-agonist protocol (1). The authors should be congratulated for their self-criticism, stating that only four RCTs were considered to be at ''low'' risk of bias whereas the remaining studies were at ''high'' or ''unclear'' risk of bias due to lacking outcome data (1).…”

“…The authors should be congratulated for their self-criticism, stating that only four RCTs were considered to be at ''low'' risk of bias whereas the remaining studies were at ''high'' or ''unclear'' risk of bias due to lacking outcome data (1). In addition, they declared that most of the included studies received support from the manufacturer of corifollitropin-a, another potential source of bias (1).…”