Mental distress and personality in women undergoing GnRH agonist versus GnRH antagonist protocols for assisted reproductive technology.
OBJECTIVE
Do mental distress and mood fluctuations in women undergoing GnRH agonist and GnRH antagonist protocols for assisted reproductive technology (ART) differ depending on protocol and the personality trait, neuroticism?


CONCLUSIONS
ART treatment did not induce elevated levels of mental distress in either GnRH antagonist or agonist protocols but neuroticism was positively associated with increased mental distress, independent of protocols.


BACKGROUND
ART treatment may increase mental distress by mechanisms linked to sex hormone fluctuations. General psychological characteristics, such as personality traits indexing negative emotionality, e.g. neuroticism, are likely to affect mental distress during ART treatment.


METHODS
A total of 83 women undergoing their first ART cycle were consecutively randomized 1:1 to GnRH antagonist (n = 42) or GnRH agonist (n = 41) protocol. The study population was a subgroup of a larger ongoing Danish clinical randomized trial and was established as an add-on in the period 2010-2012.


METHODS
Women in the GnRH antagonist protocol received daily injections with recombinant follicle-stimulating hormone, Puregon(®) and subcutaneous injections with GnRH antagonist, Orgalutran(®). Women in the GnRH agonist protocol received nasal administration of the GnRH agonist, Synarela(®) and subcutaneous injections with FSH, Puregon(®). The study design did not allow for a blinding procedure. All women self-reported the Profile of Mood States, the Perceived Stress Scale, the Symptom Checklist-92-Revised, and the Major Depression Inventory questionnaires, at baseline, at ART cycle day 35, on the day of oocyte pick-up, and on the day of hCG testing. Also, a series of Profile of Mood States were reported daily during pharmacological treatment to monitor mood fluctuations. The personality trait Neuroticism was assessed at baseline by the self-reported NEO-PI-R questionnaire.


RESULTS
ART did not induce within- or between-protocol changes in any of the applied measures of mental distress. However, the GnRH antagonist protocol was associated with more pronounced median mood fluctuations during the stimulation phase (antagonist, 11.0 SD, [IQR = 21.1-6.1]; agonist, 8.9 SD, [IQR = 11.3-5.7], P = 0.025). This association became non-significant after applying a Bonferroni-Holm correction. Neuroticism was highly positively associated with increased levels of mental distress throughout treatment independent of protocols (all P-values <0.006), and cross-sectional analysis revealed that women with high or low Neuroticism scores at baseline showed a significant trend towards lower chances of a positive pregnancy test (P-value =0.028).


CONCLUSIONS
Information on prognostic factors such as preceding length of infertility, number of retrieved oocytes and number of prior insemination treatments was not accounted for in the analyses. The stratification of protocols by age in the subgroups of women included in this study was suboptimal. Women with prior or current use of antidepressant medication were excluded from our study.


CONCLUSIONS
Our results imply that mental distress emerging during ART treatment is not causally linked to hypogonadism per se or to the choice of protocol. Rather, our data highlight the potential importance of (i) rapid increases in ovarian steroids and (ii) addressing personality traits indexing negative emotionality, i.e. Neuroticism, in women undergoing ART treatment, to optimize both emotional adjustment and, possibly, the chances of obtaining pregnancy.


BACKGROUND
The Danish Research Council for Independent Research and MSD, Denmark kindly supported the study. The authors declare no competing financial interests.


BACKGROUND
EudraCT - 2008-005452-24.
Neurobiology Research Unit, Copenhagen University Hospital and Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.
D S
DS
Stenbæk
Hvidovre University Hospital, Fertility Clinic, Copenhagen, Denmark.
M
M
Toftager
Neurobiology Research Unit, Copenhagen University Hospital and Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.
L V
LV
Hjordt
Neurobiology Research Unit, Copenhagen University Hospital and Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.
P S
PS
Jensen
Neurobiology Research Unit, Copenhagen University Hospital and Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
K K
KK
Holst
Hvidovre University Hospital, Fertility Clinic, Copenhagen, Denmark.
T
T
Bryndorf
Hvidovre University Hospital, Fertility Clinic, Copenhagen, Denmark.
T
T
Holland
Hvidovre University Hospital, Fertility Clinic, Copenhagen, Denmark.
J
J
Bogstad
Hvidovre University Hospital, Fertility Clinic, Copenhagen, Denmark.
A
A
Pinborg
Hvidovre University Hospital, Fertility Clinic, Copenhagen, Denmark.
P
P
Hornnes
Neurobiology Research Unit, Copenhagen University Hospital and Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark vibe@nru.dk.
V G
VG
Frokjaer
D000328:Adult; D000339:Affect / Q000187:drug effects; D001008:Anxiety Disorders / Q000523:psychology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D000075384:Neuroticism; D010551:Personality; D027724:Reproductive Techniques, Assisted / Q000523:psychology*; D013315:Stress, Psychological
D007987:Gonadotropin-Releasing Hormone; C061018:ganirelix
assisted reproductive technology; mental distress; neuroticism; ovarian stimulation protocol; personality