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Optimizing Ovarian Stimulation Treatment Options for Assisted Reproductive Technology
use have only modest to poor predictive value. The ideal predictive test is
Figure 2: Images of Normal (A) and Polycystic (B) Ovaries
yet to be defined.
A B
Lifestyle
Other extrinsic factors are also worthy of consideration. Obesity, as
measured using the BMI, and its secondary effects on insulin resistance
and hyperandrogenism, may also affect fertility. Dokras et al. reported a
significantly higher risk for IVF cycle cancellation in morbidly obese
patients, although BMI had no effect on clinical pregnancy or delivery rate.
Furthermore, obese and morbidly obese subjects had a significantly higher
risk for obstetric complications.
26
Cigarette smoking, alcohol, and caffeine are other lifestyle factors that
A: Reproduced with permission from Siemens Ultrasound and obgyn.net
have a negative impact on fertility. Specifically, cigarette smoking is linked B: Reproduced with permission from www.ivf-infertility.com
to elevated FSH levels, although it does not appear to affect inhibin B and
estradiol levels or antral follicle count.
27
There is compelling evidence that determined that some were more clinically useful than others. They devised
smoking has a negative influence on IVF outcome.
28
a nomogram consisting of five weighted factors—number of antral follicles,
ovarian volume, Doppler score (stromal blood flow), age, and smoking
Optimizing Treatment With Consideration to status. According to the nomogram, a 36-year-old non-smoking woman
Predictive Factors with 10 antral follicles, ovarian volume of 8ml, and a Doppler score of four
The highest success rates with IVF or ovulation induction are observed in would receive 220IU/day of FSH; a 28 year-old woman who smokes five
the first treatment cycle. Patients with the highest reproductive potential cigarettes a day and has 30 antral follicles, ovarian volume of 11ml, and a
conceive in the first one to three cycles. Choice of the appropriate starting Doppler score of six would receive 120IU/day of FSH.
protocol is important. It is not always possible to predict response in the
treatment-naïve patient and the outcome of the first protocol becomes This nomogram was then compared in a prospective randomized trial with
important in determining how to adjust subsequent treatment regimens. a standardized FSH dose in 267 patients. Retrieval of 5–14 oocytes was
Optimization of the starting dose of gonadotropins FSH is a key deemed an appropriate response. This study suggested that an
component for success. individualized dosing regimen optimized ovarian response and reduced the
need for dose adjustments during COS. A higher ongoing pregnancy rate
Normal Responders was observed in the individualized dosing group.
30
Studies of predictive factors are not always comparable owing to differences
in study design and subject characteristics. In an attempt to consolidate this Non-standard Patients—Potential Poor Responders
information, Popovic-Todorovic et al.
29
examined several of these predictive It is important to distinguish between follicular response to treatment and
factors in a single prospective study of 155 women undergoing their first overall ART success. Older women face a significant impairment in
implantation efficiency, which is largely independent of the magnitude of
their stimulation response. There are presently no treatment strategies
apart from oocyte donation that have been shown to significantly improve
Patients with the highest reproductive implantation efficiency in older women.
3,7
Nonetheless, recent efforts have
potential conceive in the first one to three
focused on the continued development of improved stimulation
protocols, the facilitation of embryo implantation through zona pellucida
cycles. Choice of the appropriate starting micromanipulation (assisted hatching), and screening pre-implantation
protocol is important.
embryos for aneuploidy,
31
among other techniques.
32
For a subset of women who have failed IVF, the use of autologous
endometrial co-culture (AECC) may be of value. This technique improves
IVF/intracytoplasmic sperm injection (ICSI) treatment cycle. Inclusion criteria embryo quality and pregnancy outcome, and Spandorfer et al.
33
showed
were normal basal FSH level, presence of both ovaries, regular menstrual that histological characteristics, including dating of the endometrium,
cycle, age less than 40 years, and absence of endocrine disorders—in other predict success following AECC. In a prospective study of 86 consecutive
words, a relatively ‘normal’ patient. All patients were started on a standard patients undergoing IVF, there was a significant improvement in embryo
gonadotropin dose of 150IU/day and measurements were taken of the quality using AECC.
number of antral follicles, ovarian volume, ovarian stromal blood flow, and
hormone levels, including E2, FSH, LH, inhibin B, and testosterone. Age, Non-standard Patients—Polycystic Ovary Syndrome
BMI, cycle length, and smoking status were also recorded. On day eight of Polycystic ovary syndrome (PCOS) is itself a predictor of infertility
34
stimulation, the response was assessed and the dose of FSH adjusted if and is also strongly related to obesity.
35
For PCOS patients in the
necessary.
29
While all the factors measured were, to a certain extent, context of IVF, there is evidence that a protocol combining an oral
independent predictors of the number of aspirated follicles, the researchers contraceptive overlapping with a GnRH agonist followed by low-dose
FERTILITY TREATMENT REVIEW 7
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