Evidence based management of poor responders
in assisted reproduction
Hassan N. Sallam, MD, FRCOG, PhD (London)
Professor in Obstetrics and Gynaecology, Alexandria University, and
Clinical and Scientific Director, Alexandria Fertility Center,
Alexandria, Egypt
It is estimated that about 10 percent of women treated with IVF and ICSI
are "poor responders", but various criteria have been used to define this
condition (Surrey and Schoolcraft, 2000). In order to establish an objective
definition, we have constructed ROC curves for our patients and found
that, based on our results, poor responders are patients from whom less
than 5, 6 or 8 oocytes are retrieved, when undergoing treatment with ICSI,
IVF or TeSE/ICSI, respectively (Sallam et al, 2005). A new definition has
also been proposed by the ESHRE Bologna group but has been widely
criticized as non evidence-based (Ferraretti et al, 2011).Various regimens
have been suggested and used for the treatment of poor responders. These
include (1) increasing the dose of HMG, (2) using purified HMG or
recFSH, (3) starting FSH stimulation in the late luteal phase, (4)
diminishing the duration of GnRHa (flare up protocols), (5) diminishing
the dose of GnRHa, (6) using GnRH antagonist (single or multiple dose
protocols), (7) performing IVF/ICSI in natural unstimulated cycles (with
or without GnRH antagonists), (8) adding clomiphene citrate, growth
hormone, testosterone, DHEA or L-arginine to HMG/FSH stimulation.
Randomised trials (RCTs) have shown that the addition of GH (Duffy et
al, 2010) or testosterone gel (Kim et al, 2011) increase the clinical
pregnancy rate significantly. In addition, in one small randomized
controlled trial, the use of recFSH may also be of benefit (Raga et al, 1999).
References:
Duffy JM, Ahmad G, Mohiyiddeen L, Nardo LG, Watson A. Growth
hormone for in vitro fertilization. Cochrane Database Syst Rev
20;(1):CD000099, Jan 2010
Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L;
ESHRE working group on Poor Ovarian Response Definition. ESHRE
consensus on the definition of 'poor response' to ovarian stimulation for in
vitro fertilization: the Bologna criteria. Hum Reprod 26(7):1616-24, 2011.
Kim CH, Howles CM, Lee HA. The effect of transdermal testosterone gel
pretreatment on controlled ovarian stimulation and IVF outcome in low
responders. Fertil Steril 95(2):679-83, 2011.
Raga F, Bonilla-Musoles F, Casan EM, et al: Recombinant follicle
stimulating hormone stimulation in poor responders with normal basal
concentrations of follicle stimulating hormone and oestradiol: improved
reproductive outcome. Hum Reprod 14(6):1431-1434, 1999.
Sallam HN, Ezzeldin F, Agameya AF, Rahman AF, El-Garem Y. Defining
poor responders in assisted reproduction. Int J Fertil Womens Med
50(3):115-20, 2005.
Surrey ES, Schoolcraft WB: Evaluating strategies for improving ovarian
response of the poor responder undergoing assisted reproductive
techniques. Fertil Steril. 73(4):667-76, 2000.