P–484 Progesterone supplementation in modified natural frozen embryo transfer (mNC-FET) does not cause mental health adverse effects - A sub-study of a multicenter RCT
Authors: Pistoljevic N , Saupstad M , Mizrak I , Andersen L F , Englund A L , Cou. Freiesleben N L , Husth M , Klajnbard A , Knudsen U B , Løssl K , Schmidt L , Pinborg A 
Published: August 2021

Abstract

Study question
Do women undergoing mNC-FET with progesterone supplementation experience mental health adverse effects at a greater rate compared to a control group.

Summary answer
Progesterone supplementation does not affect mental wellbeing in women undergoing mNC-FET.

What is known already
Women and men undergoing assisted reproductive treatment more likely to experience stress and other adverse psychological effects than the background population. Various factors such as parental age, cause of infertility and treatment method have been shown to affect patient well-being. Progesterone supplementation is known to cause various physical adverse effects, yet few studies have investigated the potential mental health adverse effects of progesterone supplementation in FET.

Study design, size, duration
This is a sub-study of an ongoing RCT investigating the effect of luteal phase progesterone supplementation in mNC-FET. The aim is to investigate possible mental health adverse effects of progesterone. From 2019–2021 a total of 164 women were included (n = 84 and n = 82 in the progesterone and control group, respectively). The health and wellbeing self-reporting survey was fulfilled after randomization on hCG trigger + 11 days.

Participants/materials, setting, methods
A validated, electronic questionnaire in Danish was used to measure mental wellbeing in women aged 18–41 years undergoing mNC-FET with and without use of progesterone supplementation in the luteal phase at seven Danish public hospitals. Women were randomized to either progesterone treatment or no progesterone by a computerized randomization algorithm with minimization for female age &gt; =37 years, previous oocyte retrievals and previous FET. Comparisons of survey responses were performed by chi-square tests.

Main results and the role of chance
The survey response rate was 68%. We observed no significant differences in any of the three items between the progesterone group and the control group. On the first item “to which degree have you felt sensitive due to treatment”, 56% and 52% responded “to a large degree” or “to some degree” sensitive in the progesterone vs. control group, while 25% and 34% vs. 19% and 13% responded “to a lesser extent” or “not at all” sensitive in progesterone vs. controls (P = 0.35).
On the second item, “to which degree have you felt aggressive due to treatment”, 10% and 9% responded “to a large degree” or “to some degree”, 29% and 22% answered “to a lesser degree” and 62% and 70% responded “not at all” in the progesterone vs control group (P = 0.57).
On the third item “to which degree have you cried unexpectedly due to treatment” 25% and 18% responded “to a large degree” or “to some degree” in the progesterone vs control group, 20% and 27% answered “to a lesser extent”, while 55% in both groups answered “not at all” (P = 0.44).

Limitations, reasons for caution
In a self-reported survey selection bias, due to a less than 100% response rate, and reporting bias cannot be excluded. However with the possibility to answer the survey online at leisure, the risk of reporting bias is minimized.
Wider implications of the findings: A large concern for clinicians working with ART is patient wellbeing. Our study suggests that luteal phase support does not cause extra emotional distress, though further research is needed.

Trial registration number
NCT03795220