Questionable recommendation for LPS for IVF/ICSI in ESHRE guideline 2019: ovarian stimulation for IVF/ICSI.

Sir,

I am grateful to the Journal for having acknowledged the error previously included in this issue concerning the “conditional” instead of “strong” recommendation of progesterone for luteal phase support after IVF/ICSI and for publishing an erratum on the Human Reproduction Open website on 29 December 2020, as a part of Human Reproduction Open, Volume 2020, Issue 4.

The ESHRE guideline development group (GDG) formulated 84 recommendations answering 18 key questions on ovarian stimulation for IVF/ICSI which are welcome and appreciated since there are, to their knowledge, no evidence-based guidelines dedicated to the process of ovarian stimulation (Bosch ; ESHRE Reproductive Endocrinology Guideline Group 2019). It is worth noting that eight comments were made in relation with luteal phase support recommendations, all processed by the GDG and released in the final publication, of which six raised by the industry questioning why “Dydrogesterone is probably recommended for luteal phase support” with a “conditional” recommendation. The GDG rediscussed, confirmed this recommendation, and “considers the safety data from 2000 patients (Lotus 1 and Lotus 2 study) insufficient to make a firm statement and there is a lack of long-term offspring health studies.” Therefore the publication summarizing the conditional recommendation for dydrogesterone by the GDG is misleading and is not reflecting at least objectively the confirmed position of the GDG as reported in the full guideline document about lack of long-term offspring health studies. Some safety concern in relation with congenital heart disease and malformations has been recently suggested in several publications in reputable peer-reviewed journals (Zaqout , 2017; Nadarajah ; Koren ; Malherbe ). Due to the crucial role of luteal phase support in IVF/ICSI procedures, we believe that this letter needs to be published in the Journal to emphasize this misleading, at least incomplete recommendation which is of particular concern given that in most European countries except the Netherlands dydrogesterone is not approved by the regulatory agencies for luteal phase support after IVF/ICSI adding to the confusion introduced by the error concerning the strong recommendation for progesterone.