The prevalence of late-follicular phase progesterone elevation and impact on the ongoing pregnancy rate after fresh and frozen blastocyst transfer. Sub-study of an RCT

Abstract

The effect of late-follicular phase progesterone elevation (LFPE) during ovarian stimulation on reproductive outcomes in ART treatment remains controversial, but recent studies indicate lower pregnancy rates with rising progesterone levels. This study aims to investigate the prevalence of late-follicular phase progesterone elevation (LFPE) and possible impact on ongoing pregnancy rate after fresh or frozen blastocyst transfer in a sub-study setting of a randomised controlled trial. A total of 288 women were included (n=137 and n=151 in the fresh transfer and freeze-all group, respectively). Among these 11(3.8%) had a progesterone level ≥1.5 ng/ml, and 20(6.9%) had a progesterone level ≥1.2 ng/ml on trigger day. Spline regression analysis showed no significant effect of late follicular phase progesterone levels on ongoing pregnancy. In the multivariate regression analysis (n = 312) only age, but not progesterone level on trigger day was significantly associated with ongoing pregnancy. In conclusion, in a clinical setting with moderate gonadotrophin stimulation and well-defined trigger and fresh transfer cancellation criteria, the prevalence of women with LFPE ≥1.5 ng/ml was low and did not indicate the clinical value of routine measurement of progesterone in the late follicular phase.

Keywords:

• Serum Progesterone
• In vitro fertilisation
• Frozen embryo transfer
• Ongoing pregnancy rate

Acknowledgements

The authors would like to thank all participating women for their contribution and all employees at the eight participating fertility clinics for helping with the recruitment for the trial: Denmark: Hvidovre, Copenhagen University Hospital, Copenhagen, Rigshospitalet, Copenhagen University Hospital, Herlev, Copenhagen University Hospital, Holbæk, Copenhagen University Hospital, Skive, Aarhus University Hospital. Sweden: Sahlgrenska University Hospital, Göteborg, Skåne University Hospital Malmö. Spain: Dexeus University Hospital, Barcelona.

Authors roles

ANA, AP, KL and SS designed the trial and wrote the study protocol. CB contributed to the revision and editing of the study protocol. AP and SS supervised the study. SS, AP, KL, ANA, NS, JB, LP, HSN, AK, ALM, NCF, CB and PH were involved in the recruitment of patients and the acquisition of data. AZ was responsible for the biobank. JL, SS and KL analysed the data. SS wrote the first draft of this manuscript. AP, SS, KL, ANA, NS, JLF, AZ, JB, LP, HSN, NCF, AK, ALM, SZ, CB and PH and were all involved in the critical revision of the manuscript. All authors approved the final version of the manuscript to be submitted.

Ethical approval

The study was approved by the Scientific Ethical Committee in the Capital Region Denmark (approval No H-1600- 1116), the Scientific Ethical Committee in Region Skäne in Sweden (approval No Dnr. 2016/654), and the Scientific Ethical Committee in Barcelona. The study is part of the Reprounion Collaborative study, co-financed by the European Union, Interreg V ÖKS. All women and couples gave written informed consent.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data collected for the study, including deidentified individual participant data and a data dictionary defining each field in the set, will be made available after publication. Requests for data sharing can be made by contacting the corresponding author. Data will be shared after review and approval by the trial scientific board and terms of collaboration will be reached together with a signed data access agreement.

Additional information

Funding

This work was supported by the Reprounion Collaborative study, co-financed by the European Union, Interreg V ÖKS under Grant 20200407. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.