An observational study of assisted reproductive technology outcomes in new European Union member states: an overview of protocols used for ovarian stimulation

Abstract

Background:

The development of new fertility treatment options has facilitated individualized assisted reproductive technology (ART) protocols to improve outcomes. Manufacturing improvements to recombinant human follitropin alfa have allowed precise dosing based on mass (filled-by-mass; FbM) rather than bioactivity (filled-by-bioassay; FbIU). Continued monitoring and reporting of follitropin alfa treatment outcomes in routine clinical practice is essential.

Objective:

To provide an overview of the frequency of different controlled ovarian-stimulation protocols used in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles in new European Union member states, and to provide post-registration efficacy and safety data on follitropin alfa.

Research design and methods:

A 2-year, prospective, observational, multicentre, Phase IV study conducted at ART clinics in the Czech Republic, Estonia, Latvia, Lithuania, Poland, Slovakia and Slovenia. Women aged 18–47 years undergoing ovarian stimulation with follitropin alfa for conventional IVF or ICSI were eligible for inclusion. The main treatment outcome was cumulative clinical pregnancy rate. Data were analysed descriptively.

Results:

Clinical pregnancy outcomes were available for 4055 of 4085 (99.3%) patients. In total, 1897 (46.8%) patients used follitropin alfa FbIU; 2133 (52.6%) used follitropin alfa FbM. Clinical pregnancy was achieved by 39.5% (1603/4055) of patients. A greater proportion of patients with polycystic ovary syndrome achieved a clinical pregnancy than those with endometriosis (41.8% vs 37.8%, respectively). A higher cumulative pregnancy rate was observed with the use of follitropin alfa FbM than follitropin alfa FbIU (41.3% vs 37.8%, respectively; p = 0.02).

Conclusions:

This study represents the most comprehensive audit of individualized ART in clinical practice in Central and Eastern Europe. Overall, clinical pregnancy was achieved by 39.5% of patients after stimulation with follitropin alfa. The use of follitropin alfa FbM resulted in a higher cumulative pregnancy rate than did the FbIU formulation. However, limitations of the study include the observational and non-comparative study design, and descriptive nature of statistical analyses; furthermore, the study was not designed to make direct comparisons between the success rates of different ovarian-stimulation protocols.

Key words::

• Assisted reproductive technology
• Audit
• Europe
• Recombinant human follicle-stimulating hormone

Transparency

Declaration of funding

Regional Mrck Serono offices sponsored this study, and assisted with data analysis and provided feedback on the manuscript. Merck Serono S.A. – Geneva, Switzerland (an affiliate of Merck KGaA, Darmstadt, Germany), funded the editorial support provided to the authors and the publication of this article.

Declaration of financial/other relationships

All the authors have disclosed that they have no relevant financial relationships.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed he is a former employee and share holder in AstraZeneca Ltd. Peer Reviewer 2 has disclosed that he has no relevant financial relationships.

Acknowledgements

The authors thank Zbigniew Braszkiewicz PhD, Evaldas Brazaitis MD, Tonko Mardesic MD and Kurt Marhardt MD for their support and coordination of the study. The authors would also like to thank Joanna Brown DPhil of Caudex Medical (financially supported by Merck Serono S.A. -- Geneva, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany) for her assistance with the writing of this manuscript.