Manipulation of the follicular phase: Uterodomes and pregnancy - is there a correlation?

Abstract

BACKGROUND: Manipulation of the follicular phase uterine epithelium in women undergoing infertility treatment, has not generally shown differing morphological effects on uterine epithelial characteristics using Scanning Electron Microscopy (SEM) and resultant pregnancy rates have remained suboptimal utilising these manipulations. The present study observed manipulation of the proliferative epithelium, with either 7 or 14 days of sequential oestrogen (E) therapy followed by progesterone (P) and assessed the appearance of pinopods (now called uterodomes) for their usefulness as potential implantation markers in seven women who subsequently became pregnant. Three endometrial biopsies per patient were taken during consecutive cycles: day 19 of a natural cycle - (group 1), days 11/12 of a second cycle after 7 days E then P - (group 2), and days 19/22 of a third cycle after 14 days E then P - (group 3). Embryo transfer (ET) was performed in a subsequent long treatment cycle (as per Group 3). RESULTS: Seven pregnancies resulted in seven viable births including one twins and one miscarriage. Analysis of the individual regimes showed 5 days of P treatment to have a higher correlation for uterodomes in all 3 cycles observed individually. It was also observed that all 7 women demonstrated the appearance of uterodomes in at least one of their cycles. CONCLUSIONS: We conclude that manipulation of the follicular phase by shortening the period of E exposure to 7 days, does not compromise uterine epithelial morphology and we add weight to the conclusion that uterodomes indicate a receptive endometrium for implantation.

Figure 1

Scanning electron micrographs of 3 biopsies from the same patient (no. 5) demonstrates the variable response of the epithelium to exogenous hormone supplementation. (A) suboptimal epithelial appearance for D5 natural cycle displaying variable morphology of flattened, pleiomorphic cells without cell borders, variable microvilli coverage and structure and few cilia groups. (B) D5 of the short E2 cycle shows an abundance of fully developed uterodomes, (C) D7 of long E2 cycle shows developing uterodomes. Scale bar = 10 μm.

Figure 2

Scanning electron micrographs of the same patient (no. 1) demonstrates a shift in the nidation window with exogenous hormones. (A) An abundance of fully developed uterodomes are shown on D5 of the natural cycle. (B) D8 long E2 shows retarded epithelium suggestive of pinopod appearance 1-2 days later. Note clumping of swollen microvillous tips on protruding cells and secretory droplets. Scale bar = 10 μm.

Figure 3

Scanning electron micrographs from the same patient (no. 7) at D5 in different cycles demonstrated an increase in abundance of uterodomes utilising exogenous hormones. Scale bar = 10 μm. (A) Epithelium displaying few uterodomes in the natural cycle (B) An increase in abundance of uterodomes after hormone supplementation is observed.