The developmental capacity of human in vitro matured oocytes retrieved from small antral follicles (4-6 mm) in non-hCG-primed cycles

Introduction: Priming with human chorionic gonadotrophin (hCG) before
oocyte retrieval is a common strategy in oocyte in vitro maturation (IVM) treatment.
Although this approach may have a beneficial effect on the number of
oocytes retrieved and on oocyte maturation rates, hCG may disrupt important
signaling processes at the oocyte-somatic cell interface during oocyte maturation
in vitro, and there is no strong evidence that hCG triggering leads to higher
pregnancy rates in patients with polycystic ovary syndrome (PCOS). In these
patients, an important number of cumulus-oocyte complexes (COCs) obtained
during oocyte retrieval are aspirated from small antral follicles with a mean
diameter between 4 and 6 mm. We investigated whether oocytes derived from
these small antral follicles can produce embryos that implant after maturation
in an IVM system without hCG priming.
Material and Methods: Between January and December 2010, 96 IVM-treatment
cycles were performed at UZ Brussel in patients with PCOS. Patients
were administered an average cumulative dose of 510 ± 190 IU uFSH or HPHMG
daily before oocyte retrieval. When endometrial thickness was at least
5 mm, the oocyte retrieval was scheduled on the following day. No hCG trigger
was given. In 33 of these cycles, all follicles were between 4 and 6 mm diameter
and no dominant follicle was present at the moment of oocyte retrieval. COCs
were retrieved and cultured in IVM culture medium suite (ORIGIO) for 38 hrs
at 5% CO2 and 20% O2. After IVM, oocytes were denuded and ICSI was performed
at one time point (one hour after denuding). Maturation rate, in vitro production
of embryos and clinical outcomes after embryo transfer were evaluated.
Results: The mean age of the patients was 28.5 ± 3.9 years. All COCs were retrieved
from follicles with a diameter between 4 and 6 mm. In total, 587 COCs
(with an average of 17.8 ± 10.2 COCs / cycle) were obtained, from which 287
(48.9%) were at metaphase II (average 8.7 ± 5.3 COCs / cycle) after 38 hours of
IVM. The mean fertilisation rate was 63% (average 5.6 ± 3.3 / cycle). On day 3
after ICSI, 50% of embryos (average 2.9 ± 2.3 / cycle) had a good morphological
quality (more than 6 cells and classified as grade 1 or 2) and were eligible for transfer.
In five cycles (15%), no embryo transfer was performed due to poor embryo
quality. In 28 cycles, an embryo transfer was performed on day 3 after ICSI, with
an average of 1.29 ± 0.46 embryos per transfer. Four ongoing pregnancies (clinical
pregnancy rate of 14.2%) were established and two healthy babies were born.
Conclusion: PCOS patients represent a heterogeneous group. In a subset of these
patients, follicular development is arrested at the small antral follicular stage, and
follicles do not grow beyond 6 mm diameter despite uFSH or HP-HMG priming in IVM treatment cycles. In an IVM system without hCG-priming before oocyte
retrieval, the oocytes derived from these small follicles can complete meiosis in
vitro, be fertilised, and develop into healthy offspring. Further research is needed
to optimise the clinical and laboratory protocol of IVM treatment, tailored to the
specific follicular constellation of the ovary in patients with PCOS.

Jaar van publicatie:2011

Trefwoorden:matured oocytes, antral follicles