The controversy in conventional stimulation in DOR
It is a challenge for DOR patients to achieve pregnancy, no matter which
protocol applied to IVF. A continuing interest has been vested in DOR
research worldwide and many attempts have been made to improve IVF
outcomes. Athanasios Papathanasiou et al[12]reports that in a comprehensive review undertaken of RCTs on ‘poor
responders/DOR’ published in the last 15 years, The most popular
stimulation protocols investigated in such patients are the antagonist
protocol, the micro dose flare protocol and the long down-regulation
protocol. However, RCTs on popular protocols for poor responders or DOR
have reported conflicting results with regard to oocyte yields and
reproductive outcomes.
There has been controversy on whether increasing gonadotrophins
stimulation doses would improve IVF outcomes. Many studies showed that
large gonadotrophins doses do not increase total number of eggs
harvested and the number of mature eggs, and there were also no
differences clinical pregnancy rates and live birth rates in women with
DOR[13]. Several large RCT found incremental doses
of FSH to have a direct correlation with the number of oocytes
recovered, but with no increment in the number of good-quality
blastocysts[14]. Furthermore, the
blastocyst/oocyte ratio and fertilization rate demonstrated an inverse
relationship with the dose of stimulation[15-16].
Federica Di Guardo concluded that in DOR context, natural cycle/modified
natural cycle–in vitro fertilization, as a ‘milder’ approach, could be
a reasonable alternative to high-dose/conventional ovarian stimulation
in poor ovarian responders, with the aim to retrieve a single oocyte
with transferred to a more receptive
endometrium[17]. However, even today, many
clinicians still believe that higher stimulation doses improve outcomes
in poor responders, despite much recent data challenging this view.
Studies show that the concentration of oxidative stress parameters
significantly rose after ovarian stimulation. Superoxide generated in
the ovary induces apoptosis of granulosa cells to break down follicular
walls leading a worsened oocyte quality[18]. Some
researches on oxidative stress also indicated that controlled ovarian
hyper-stimulation can lead to disruption of oxidative-antioxidative
balance in follicle cells and oocytes, which is similar as the aging
related changes.