Introduction
The birth of the first IVF baby resulted from the transfer of single
embryo from a spontaneous ovulation cycle by Steptoe and Edwards in
1978. Soon after this ground breaking event, controlled ovarian
hyperstimulation (COH) was introduced. The availability of a high number
of oocytes facilitated the pregnancy rate of IVF treatment. However,
after more than forty years of experience, there are still women who
respond poorly to stimulation, resulting in only few oocytes at
retrieval, a reduced number of embryos available for transfer and a poor
pregnancy rate. The prevalence of poor ovarian responders among
infertile women is reported to vary between 5.6% and 35.1% depending
on differences in the definition of poor ovarian response but according
to recent reviews, it seems to have slightly increased (6, 23). Though
there might be numerous causes for the poor ovarian response. The
European Society for Human Reproduction and Embryology (ESHRE) working
group on poor ovarian response (POR) has finally given a common
definition of “poor responder,” where at least two of the following
three features must be present: (a) advanced maternal age or any other
risk factor for POR; (b) a previous POR; and (c) an abnormal ovarian
reserve test.
In the field of assisted reproductive technologies great steps forward
have been made in recent years in terms of clinical knowledge and
technological development especially in IVF laboratories. One of the
fundamental steps to success is still related to the number of oocytes
retrieved after hormonal stimulation. In fact, with lower number of
retrieved oocytes, fewer embryos are there to be selected and
transferred and thus lower pregnancy rates per transfer and lower
cumulative pregnancy rates per started cycle. Ovarian follicles mature
over a period of approximately 2–4 months. Ovarian stimulation in IVF
cycles has traditionally been focused on the stimulation of antral
follicles, which develop during the last 2 weeks of this maturation
process, to increase the number of mature follicles for oocyte
retrieval. However, successful ovarian stimulation with gonadotrophins
is limited by the requirement of the presence of multiple antral
follicles (1). The stimulation and synchronization of earlier follicles
prior to traditional ovarian stimulation may thus further improve IVF
outcomes, particularly for poor responders (21). The follicles require
about 6–8 weeks after the initiation of androgen supplementation to
achieve synchronization and become mature enough to respond to ovarian
stimulation with gonadotrophins (14, 15, 16). Based on this, many
patients could potentially benefit from androgen supplementation(DHEA)
beginning weeks or months prior to starting their IVF cycle.
The beneficial effect of metformin on ovulation induction with
clomiphene in clomiphene-resistant and obese women with polycystic ovary
syndrome was originally reported in 1998 (22). Metformin is a drug that
affects metabolism and induces ovulation by reducing the circulating
concentration of insulin. Onset of metformin is slow and gradual. To
clinically improve ovulation, it may require up to 6 months of treatment
with metformin.
In present study, we aim to investigate the impact of adjuvant agents:
DHEA and Metformin on the number of oocytes retrieved, pregnancy rates
and live birth rates in the poor ovarian responders. The differences in
the effect of adjuvant agents on IVF outcomes between the aged and the
younger poor responders were compared. This study could be helpful in
determining the influence of DHEA and metformin on controlled ovarian
hyperstimulation.