Rosenwaks.qxp 5/10/07 10:25 Page 5
The Value of Predictive Factors in Optimizing Ovarian Stimulation
Treatment Options for Assisted Reproductive Technology
a report by
Zev Rosenwaks, MD
Director, The Center for Reproductive Medicine and Infertility, Weill Cornell Medical College/NewYork–Presbyterian Hospital, New York, NY
Successful outcomes following assisted reproductive technology (ART) The 2004 Centers for Disease Control (CDC) database indicates that per
are largely dependent on the patient’s response to controlled ovarian cycle live birth rates vary significantly between age groups (from 43% for
stimulation (COS), vis à vis the number and quality of oocytes obtained women aged <35 to 6% in women >42 years of age).
It is of interest to note
and ultimately the number of embryos available for transfer. Given the that many women over the age of 40 continue to pursue fertility treatments
marked variability in ovarian response among in vitro fertilization (IVF) utilizing their own oocytes. According to a recent report, in excess of 4,000
patients, the choice of stimulation protocol must be individualized, both IVF cycles in the US were initiated in women over the age of 42.
for women with a history of prior cycles and for first-time IVF patients. live birth rate seen in older women is also a result of the increased incidence
of miscarriages (pregnancy losses approach 45% by 43 years).
Approximately 4,000–5,000 ovarian stimulation cycles are performed
annually at The Center for Reproductive Medicine and Infertility (CRMI), In a review of a large series of consecutive IVF pregnancies (with
equally divided between IVF and ovulation induction (OI). Patients documented fetal cardiac activity), Spandorfer et al.
clearly demonstrated a
frequently come to the CRMI following unsuccessful, and often multiple linear increase in miscarriage rates with advancing maternal age. Eighty-two
cycles at other clinics in the US and abroad. Approximately half of our percent of the pregnancy losses in women aged ≥40 years were associated
patients are older than 38 years and a third are over 40 years. with chromosomally abnormal fetuses (predominantly trisomies).
There are several factors that can predict the ovarian response to COS The reduced fertility associated with aging is primarily associated with aging
and, therefore, the likelihood of success following ART (see Table 1, page of the ovaries and oocytes, rather than of the uterus and endometrium. This
6), however, there are no absolutes in this regard. The objective of this was underscored by the observation that donor oocyte cycles resulted in
paper is to review the current understanding of these factors and how high pregnancy rates among recipient women, irrespective of their age (see
they might be used in practice to optimize individual stimulation protocols Figure 1, page 6).
However, in a recent large analysis of women receiving
while minimizing potential complications. donor oocytes, Toner et al.
demonstrated that while overall success rates
are constant for recipients ranging from their mid-20s through to late 40s,
Factors Predictive of Ovarian Response beyond 48 years they decline precipitously.
Age Assessment of Ovarian Reserve
Age is the most important factor in determining success rates after IVF.
The only direct method for quantifying follicle numbers and hence
As the average age of our patients has increased, the age-related decline ovarian reserve is through an ovarian biopsy.
However, the risk–benefit
in fecundity has increasingly become a dominant cause of subfertility.
ratio of this procedure does not warrant its use for clinical evaluation of
The loss of fecundity with age appears to be a consequence of both reproductive aging.
oocyte depletion and reduced oocyte quality. We have previously
demonstrated that maternal age can predict over 80% of IVF success.
A less invasive method of assessing ovarian reserve is through the
sonographic determination of either the ovarian volume or the antral follicle
count (see Figure 2, page 7). Ovarian volume is estimated using transvaginal
Zev Rosenwaks, MD, is the Director of The Center for
Reproductive Medicine and Infertility, an infertility clinic at New
ultrasound, with measurements in three planes and application of the
York Weill-Cornell. He is also Professor of Obstetrics and formula V = D1 x D2 x D3 x 0.523, with D1, D2, and D3 representing the
Gynecology at Weill Medical College of Cornell University. Dr
maximal longitudinal, antero-posterior, and transverse diameters. Mean
Rosenwaks is a diplomate of the American Board of Obstetrics
and Gynecology, and received his subspecialty certification in
ovarian volume is the mean volume calculated for both ovaries in an
reproductive endocrinology in 1981. Throughout his career, he individual patient.
has been instrumental in developing new fertility-enhancing
protocols and the study of advanced recombinant-derived
In a study by Lass et al.,
gonadotropins to assist in producing mature, high-quality sperm and eggs. Dr Rosenwaks first
the mean ovarian volume in 140 patients
developed egg donation in the US, which has made it possible to answer many important varied from 0.5 to 18.9cm
and the authors concluded that there was
questions about human reproduction. He has authored 317 scientific papers, 58 book chapters,
a strong association between ovarian volume and ovarian reserve. In a
and six textbooks.
second study by Syrop et al.,
ovarian volumes were determined prior to
pituitary down regulation. The median ovarian volume of the smaller of
© TOUCH BRIEFINGS 2007
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