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 et al., 2020; 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 et al.,2015, 2017; Nadarajah et al.,2017; Koren et al.,2020; Malherbe et al.,2020). 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.
References
- ESHRE Reproductive Endocrinology Guideline Group. Ovarian Stimulation for IVF/ICSI. Guideline of the ESHRE. Oct 2019. https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Ovarian-Stimulation-in-IVF-ICSI (13 December 2020, date last accessed).
- Koren G, Barer Y, Kaplan YC. Fetal safety of medications used in treating infertility. Expert Rev Clin Pharmacol 2020;13:991–1000. [DOI] [PubMed] [Google Scholar]
- Malherbe J, Garas G, Khor T, MacQuillan G. Delayed fulminant hepatic failure from dydrogesterone-related in vitro fertilization therapy requiring liver transplantation during pregnancy. Am J Case Rep 2020;21:e925690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nadarajah R, Rajesh H, Wong KY, Faisal F, Yu SL. Live birth rates and safety profile using dydrogesterone for luteal phase support in assisted reproductive techniques. Singapore Med J 2017;58:294–297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, Kolibianakis E, Kunicki M, Marca AL, Lainas G, Clef NL, The ESHRE Guideline Group on Ovarian Stimulation et al. Erratum: ESHRE guideline: ovarian stimulation for IVF/ICSI. Hum Reprod Open 2020;2020:hoaa067. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zaqout M, Aslem E, Abuqamar M, Abughazza O, Panzer J, De Wolf D. The impact of oral intake of dydrogesterone on fetal heart development during early pregnancy. Pediatr Cardiol 2015;36:1483–1488. [DOI] [PubMed] [Google Scholar]
- Zaqout M, Aslem E, Abuqamar M, Abughazza O, Panzer J, De Wolf D. Association between oral intake of dydrogesterone during early pregnancy and congenital heart disease: a case-control study. Lancet 2017;390:S8. [Google Scholar]