The impact of using the combined oral contraceptive pill for cycle scheduling on gene expression related to endometrial receptivity.
OBJECTIVE
Does the combined oral contraceptive pill (COCP) change endometrial gene expression when used for cycle programming?


CONCLUSIONS
COCP used for scheduling purposes does not have a significant impact on endometrial gene expression related to endometrial receptivity.


BACKGROUND
Controversy exists around COCP pretreatment for IVF cycle programming, as some authors claim that it might be detrimental to the live birth rate. Microarray technology applied to the study of tissue gene expression has previously revealed the behavior of genes related to endometrial receptivity under different conditions.


METHODS
Proof-of-concept study of 10 young healthy oocyte donors undergoing controlled ovarian stimulation (COS) recruited between June 2012 and February 2013.


METHODS
Microarray data were obtained from endometrial biopsies from 10 young healthy oocyte donors undergoing COS with GnRH antagonists and recombinant FSH. In group A (n = 5), COCP pretreatment was used for 12-16 days, and stimulation began after a 5-day pill-free interval. Stimulation in group B (n = 5) was initiated on cycle day 3 after a spontaneous menses. Endometrial biopsies were collected 7 days after triggering with hCG.


RESULTS
No individual genes exhibited increased or decreased expression (fold change (FC) >2) in patients with prior COCP treatment (group A) compared with controls (group B). However, the results of the functional analysis showed a total of 11 biological processes that were significantly enriched in group A compared with group B (non-COCP).


CONCLUSIONS
The Endometrial Receptivity Array (ERA) has only been validated on endometrial samples obtained in natural cycles and after hormonal replacement treatment (HRT). Therefore, it was not possible in this study to classify the endometrial samples as receptive or non-receptive. We used the ERA to focus on 238 genes that are intimately related to endometrial receptivity, thus simplifying the analysis and understanding of the data.


CONCLUSIONS
Cycle scheduling is common in IVF units and is used to avoid weekend retrievals and/or to distribute evenly the workload for better efficiency. Our failure to detect any relevant changes in the genes related to the window of implantation when cycles were programmed with COCP pretreatment suggests that, despite controversial clinical results in previous studies, the use of COCPs in this way does not affect uterine receptivity adversely.


BACKGROUND
Funding for this study was provided by an unrestricted grant from Merck Sharp & Dohme. C.S. and A.P. are co-inventors (with Patricia Diaz-Gimeno) of the Endometrial Receptivity Array and hold the patent. The other authors have no conflicts of interest to declare.


BACKGROUND
EudraCT registration number is 2011-003250-34.
Instituto Valenciano de Infertilidad, Av. Del Talgo 68 (28023), Madrid, Spain.
Alfonso
A
Bermejo
Carlos
C
Iglesias
María
M
Ruiz-Alonso
David
D
Blesa
Carlos
C
Simón
Antonio
A
Pellicer
Juan
J
García-Velasco
D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D010064:Embryo Implantation; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010062:Ovulation Induction / Q000379:methods*; D055815:Young Adult
D003277:Contraceptives, Oral, Combined
GnRH antagonist; contraceptive pill; cycle programming; endometrial receptivity; gene expression