The Frequency of Ovarian Hyperstimulation Syndrome and Thromboembolism with Originator Recombinant Human Follitropin Alfa (GONAL-f) for Medically Assisted Reproduction: A Systematic Review.

BACKGROUND

Recombinant human follitropin alfa (r-hFSH) is used for ovarian stimulation as part of medically assisted reproduction. There is a risk for ovarian hyperstimulation syndrome (OHSS) with r-hFSH treatment, and an increased risk for thromboembolic events in the presence of pregnancy with OHSS.

OBJECTIVES

To report the frequency of OHSS and thromboembolism with originator follitropin alfa (GONAL-f) based on the Global Safety Database of Merck KGaA, Darmstadt, Germany and a systematic review of published data.

DATA SOURCES

Reports of OHSS and thromboembolism were obtained from the Global Safety Database of Merck KGaA, Darmstadt, Germany from 20 October 1995 to 19 October 2018. The systematic review was based on MEDLINE and Embase searches from inception to 19 October 2018.

STUDY ELIGIBILITY CRITERIA

Patients receiving GONAL-f for ovulation induction or ART, with a starting dose within the range included in the prescribing information and providing information on the occurrence of OHSS and/or thromboembolism.

STUDY APPRAISAL AND SYNTHESIS MATCHES

In the Global Safety Database of Merck KGaA, Darmstadt, Germany there were an estimated 16,525,975 treatment cycles since 20 October 1995; 1110 reported cases of OHSS and 80 reported cases of thromboembolic events (reporting rates 6.7 and 0.48 per 100,000 treatment cycles, respectively). The systematic review identified 45 studies (5186 patients exposed to GONAL-f; 5240 treatment cycles). There were 272 reports of OHSS (5190 [5.19%] per 100,000 treatment cycles), including 10 cases of severe OHSS (191 [0.19%] per 100,000 treatment cycles).

LIMITATIONS

There may be the potential for under-reporting of safety outcomes in the literature, and under-reporting is a well-known phenomenon in spontaneous reporting databases.

CONCLUSION AND IMPLICATIONS OF KEY FINDINGS

Our analyses demonstrate low rates of OHSS and thromboembolism with GONAL-f.