Endometrial signaling pathways during ovarian stimulation for assisted reproduction technology

Endometrial hormone receptor expression was altered during ovarian stimulation cycles and was independent from serum E2 levels.

Laura Detti, M.D., Rebecca A. Uhlmann, M.S., Nicole M. Fletcher, B.S., Michael P. Diamond, M.D., Ghassan M. Saed, Ph.D.

Volume 100, Issue 3, Pages 889-894, September 2013


To determine the effects of different hormonal levels on endometrial biochemical development during ovulation induction for assisted reproduction technology (ART) cycles.

Prospective controlled study.

University center.

Nine women during a natural cycle (control) and 9 oocyte donors (treated) during an ART cycle.

At the time consistent with day 3 embryo transfer (LH+5 in control, hCG+5 in treated), transvaginal ultrasound, endometrial biopsy, and blood sampling were performed. Real-time reverse-transcription polymerase chain reaction was used to measure mRNA levels for insulin receptor (InsR), type I IGF receptor (IGFRI), prolactin receptor (PRL-R), androgen receptor (AR), TSH receptor (TSHR), nuclear receptors for T3 and T4 (TRα1, TRα2, and TRβ1), iodothyronine deiodinase (DIO2), and 1,25-dihydroxyvitamin D3 receptor (VDR) in the endometrial tissue.

Main Outcome Measure(s):
Biochemical endometrial development.

IGFRI mRNA levels were 69% lower in treated patients than in control subjects, 0.12 ± 0.005 pg/μg RNA versus 0.39 ± 0.01 pg/μg RNA. TSHR mRNA was 57% lower, 2.6 ± 0.1 fg/μg RNA versus 6.0 ± 0.2 fg/μg RNA. TRα1 and TRα2 mRNA did not change, but TRβ1 mRNA levels were 63% higher. DIO2 mRNA was 63% lower, 1.2 ± 0.07 pg/μg RNA versus 3.2 ± 0.2 pg/μg RNA. InsR mRNA levels, despite being 68% lower in treated patients, did not reach significance, and PRL-R, AR, and VDR did not significantly change.

Exposure of the endometrium to ovarian stimulation appears to influence insulin and thyroid hormone signaling pathways in the decidua at day 3 embryo transfer, whereas prolactin, androgen, and vitamin D pathways are uninfluenced. These findings echo the known delayed endometrial maturation during ovarian stimulation.

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