Endometrial signaling pathways during ovarian stimulation for assisted reproduction technology.

OBJECTIVE: To determine the effects of different hormonal levels on endometrial biochemical development during ovulation induction for assisted reproduction technology (ART) cycles. DESIGN: Prospective controlled study. SETTING: University center. PATIENT(S): Nine women during a natural cycle (control) and 9 oocyte donors (treated) during an ART cycle. INTERVENTION(S): 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. RESULT(S): 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. CONCLUSION(S): 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.