Randomisation
This study is a blind randomized control trial to evaluate the association between
Ova-Max intake and the quality of oocytes retrieved after ovarian stimulation.
Randomization will be performed at least three months prior to initiation of treatment
and patients will be assigned to either Ova-max or placebo by a computer-generated
randomization list.
Ovarian Stimulation
A standard ovarian stimulation protocol for all patients will be followed with 200-300 IU
of recombinant FSH and GnRH antagonist starting on day 5 of stimulation.
Induction of final oocyte maturation will be performed by recombinant hCG or GnRH
agonist. Women who are planned for fresh embryo transfer, will be administered
subcutaneous progesterone for luteal phase support starting on the day of oocyte
retrieval.
Oocyte Quality Assessment
After oocyte retrieval the cumulus cells of the Cumulus Oocyte complex (COC) are removed
and quality of all mature, metaphase II (MII) oocytes is assessed according to the
following parameters:
Oocyte shape
Oocyte size
Ooplasm characteristics
Structure of the perivitelline space (PVS)
Zona pellucida (ZP) and
Polar body (PB) morphology
Each parameter is graded as worst (-1), average (0), or best (1) and a total oocyte score
(TOS) is calculated by summing up individual parameter assessments.
The maximal TOS of an oocyte, therefore, could be +6, the lowest -6.
The 6 individual parameters are assessed in detail as follows:
Oocyte shape (-1): poor oocyte morphology (dark general oocyte coloration and/or
ovoid shape) (0): almost normal (less dark general oocyte coloration and less ovoid
shape) (+1): normal
Oocyte size (-1): abnormally small or large oocyte (0): almost normal size (+1):
oocyte size was within normal range
Ooplasm characteristics (-1): very granulated and/or very vacuolated cytoplasm
and/or demonstrated several inclusions (0): slightly granular and/or demonstrated
only few inclusions (+1): absence of granularity and inclusions
Structure of the perivitelline space (PVS) (-1): abnormally large PVS, absence of
PVS or very granular PVS (0): moderately enlarged PVS and/or small PVS and/or a less
granular PVS (+1): normal size PVS with no granules
Zona pellucida (ZP) (-1): very thin or thick ZP (0): small deviation from normal
(+1): normal zona
PB morphology (+1): flat and/or multiple PBs, granular and/or either abnormally
small or large PB (0): fair but not excellent PB (+1): normal size and shape of PB
After having assessed the TOS of all MII oocytes, the Mean Oocyte Score (MOS) of the
patient is calculated by dividing the sum of all TOS of the patient by the number of her
oocytes.
Statistical analysis
Group sample sizes of 79 and 79 achieve 80% power to detect a difference of -1.0 between
the null hypothesis that both group TOS means are -1.1 and the alternative hypothesis
that the mean TOS of the Ova-Max group is -0.1, with known group standard deviations of
2.2 and 2.2 and with a significance level (alpha) of 0.05000 using a two-sided
Mann-Whitney test assuming that the actual distribution is uniform