Safety of Follitropin Alfa/Lutropin Alfa for Stimulation of Follicular Development

Abstract

IntroductionRecombinant human luteinizing hormone (r-hLH) is used in a fixed-ratio combination with recombinant human follicle-stimulating hormone (r-hFSH) for the stimulation of follicular development.ObjectiveThe objective of this article was to conduct a review of safety data to evaluate the risks of r-hFSH/r-hLH treatment.MethodsData were retrieved from the Global Safety Database (Merck KGaA, Darmstadt, Germany) including reports from healthcare professionals, patients, health authorities, clinical trials, non-interventional studies, and the literature. Reports of important risks (identified and potential) as per the risk management plan applicable at the time of data retrieval were obtained up to December 2017. The estimated patient exposure to r-hFSH/r-hLH in the post-marketing setting was 427,012 treatment cycles. Nine hundred patients received r-hFSH/r-hLH during company-sponsored clinical trials (pre- and post-marketing).ResultsWe identified 72 case reports describing important risks related to r-hFSH/r-hLH use, including 46 cases of ovarian hyperstimulation syndrome (10.8 per 100,000 treatment cycles) and 24 of hypersensitivity reaction (5.6 per 100,000 treatment cycles). No thromboembolic events were reported. One congenital anomaly, not suspected to be related to r-hFSH/r-hLH use, was reported during a clinical trial; the event was resolved by corrective surgery. Two fatal cases were identified; one case of recurrent malignant melanoma (suspected to be related to r-hFSH/r-hLH use) and one case resulting from complications of ovarian hyperstimulation syndrome.ConclusionCumulative reporting rates of important identified and potential risks of r-hFSH/r-hLH during a 10-year surveillance period demonstrate the benefit–risk balance is positive. This post-marketing surveillance and continued surveillance of safety events should provide reassurance about the use of r-hFSH/r-hLH in clinical practice.Electronic supplementary materialThe online version of this article (10.1007/s40264-018-0742-3) contains supplementary material, which is available to authorized users.

Use of a recombinant human follicle-stimulating hormone:recombinant human luteinizing hormone (r-hFSH:r-hLH) 2:1 combination for controlled ovarian stimulation during assisted reproductive technology treatment: A real-world study of routine practice in the Russian Federation

“…Mild OHSS was reported in four patients who received an embryo transfer, all of which resolved. There were no deaths reported in this study, and the safety results are consistent with the known safety profile of the r-hFSH:r-hLH 2:1 combination [4,38]. Therefore, the higher pregnancy rates observed in the current study were not accompanied by an increased risk of OHSS, and the incidence of OHSS was similar to that observed in the ESPART trial (<1% of patients in both studies) [6].…”

Female melanoma and estrogen receptors expression: an immunohistochemical pilot study

“…Three of these subjects in the group of OS had been treated before the development of CM with follitropin alfa injections to stimulate ovarian follicular development (range 1–9 years before). Anecdotally, in one patient, this drug intake was associated with recurrent CM [27]. Nevertheless, there is no proven evidence of a higher CM risk after ART [28].…”

Mini review: The FDA‐approved prescription drugs that induce ovulation in women with ovulatory problems

“…However, recent data suggested that compared to follitropin alfa, corifollitropin alfa (Elonva) as the first hybrid FSH molecule (with a longer half‐life compared with FSH) could facilitate IVF treatment in women with impaired ovarian reserve or poor ovarian response (POR) undergoing intracytoplasmic sperm injection (ICSI) procedure (de Lartigue, 2011; Kolibianakis et al, 2015; Loutradis, Drakakis, Vlismas, & Antsaklis, 2009). Common side effects of follitropin include headache, nausea, vomiting, mild stomach/abdominal pain, pelvic pain, tenderness, bloating breast, swelling, and tenderness pain (Abramova et al, 2019; Kurji et al, 2019).…”