Endometrium receptivity in in-vitro maturation (IVM) treatment: in need of improvement.

Introduction: Despite recent technical advances to the laboratory protocol of
in vitro maturation of oocytes (IVM), implantation rates after IVM are still
lower than in conventional ART. Typically, the abrogated follicular phase and
the absence of functional corpora lutea compromise the follicular and luteal sex
steroid production and preclude the development of a receptive endometrium.
Therefore, most clinical IVM protocols rely on the use of estrogen and progesterone
supplementation for endometrial preparation. However, studies focusing
on the implantation potential of the endometrium in IVM-cycles are scarce.
Material and Methods: Between February 2009 and December 2010, endometrium
quality in the luteal phase of IVM cycles was prospectively assessed by a
single observer using vaginal ultrasound scanning and histological analysis of endometrium
biopsies performed on day 5 or 6 after immature oocyte retrieval (OR).
This schedule would coincide with the transfer of a cleavage-stage embryo after
IVM and ICSI. 67 healthy egg donors (54 with regular cycles and 13 with polycystic
ovarian syndrome (PCOS)) and 18 patients with PCOS, who underwent elective
freezing of all embryos, underwent a total of 100 IVM cycles. Endometrial
priming consisted of 450 IU uFSH or HP-HMG, followed by 6 mg daily transdermal
estradiol gel (10 mg if endometrium thickness was <8 mm), started on the day
before OR, and 600 mg daily vaginal progesterone from the day of OR onwards.
In 69 cycles, no hCG-priming was given; in 11 cycles, participants received a final
oocyte maturation trigger using 5,000 IU hCG 36 hours prior to hCG. In 20 further
cycles, a single bolus of 1,500 IU hCG was administered 6 hours after OR.
Results: In individuals with PCOS and according to Noyes' criteria, 33,3%
(4/12) of representative endometrium biopsies in non-hCG-primed IVM cycles
showed a mid-secretory morphology and 50% (6/12) showed early secretory
features. In hCG-primed cycles in PCOS individuals, 39% (7/18) showed midsecretory
changes and 50% (9/18) of biopsies were reported as early-secretory
endometrium. 11% (2/18) showed no secretory changes.
In non-hCG-primed IVM cycles in oocyte donors with regular cycles
and normal ovaries, 33.3% (16/48) of representative endometrium biopsies
showed a mid-secretory morphology, 43.8% (21/48) were early-secretory and
18.8% (9/48) had no secretory changes. In hCG-primed IVM cycles in oocyte
donors with regular cycles and normal ovaries, 75% (9/12, p = 0.019) and 25%
(3/12) showed a mid- resp. early-secretory endometrium. With an average of
7.46 ± 3.27 mm in mid-secretory and 7.44 ± 2.49 mm in early-secretory endometrium,
endometrium thickness did not correlate with histology.
Conclusions: A receptive, mid-secretory endometrium is a prerequisite for successful
implantation. Although endometrial assessment based on the histologic
appearance using morphologic markers has been shown to have limitations,
the histological findings of the study presented here show a high incidence of a
secretory delay of the endometrial development in spite of standard hormonal
priming. We found a tendency toward improved endometrial receptivity in
hCG-primed IVM-cycles, at least in non-PCOS individuals. Based on the currently
available data, further research is needed to establish an optimal protocol
for endometrial priming in IVM-cycles and should be focused on the improvement
of IVM culture systems, to result in higher blastocyst transfer rates, and
on the efficacy of a freeze-all embryos policy, followed by warming and transfer
in an adequately prepared endometrium of an artificial cycle.

Jaar van publicatie:2011

Trefwoorden:In vitro maturation, endometrium