CHICAGO – Transabdominal antral follicle count measurements are obtainable in girls as young as 4 years and were highly correlated with serum anti-müllerian hormone assays in a cross-sectional substudy.
"These may prove to be very useful measurements of ovarian reserve in these young girls, as they are in reproductive-aged women," lead author Dr. Amber R. Cooper said at the annual meetingof the North American Society for Pediatric and Adolescent Gynecology.
Ovarian reserve screening is frequently used to predict response to gonadotropin stimulation during assisted reproductive technology treatment and for counseling adult women on their overall chance for conception. Data are very scarce on measures of ovarian reserve in premenarchal girls, although several factors such as chemotherapeutic agents, radiation, environmental triggers, and underlying genetic conditions can potentially threaten the oocyte pool and thus fertility.
Dr. Amber R. Cooper
"There are a lot of patients that you can potentially consider using ovarian reserve screening [for], and in a much younger age group than you probably anticipated," she said. "Those that may have a larger threat to their oocyte pool may ultimately, as technology progresses, warrant discussion about fertility preservation options."
Dr. Cooper and her colleagues screened ovarian reserves at scheduled intervals over a 2-year period in 41 premenarchal girls, aged 4-14 years, who were enrolled in an ongoing prospective study of juvenile and adult rheumatoid arthritis. The girls were subdivided into prepubertal and pubertal based on the onset of breast development. Antral follicle counts were obtained using transabdominal ultrasonography (2-5 MHz) when the patients had a full bladder, and were compared with mean ovarian volume, serum anti-müllerian hormone (AMH) level measured by Elisa assay, and follicle stimulating hormone level. Data from the ongoing parent trial on 31 menarchal girls, within 3 years of menarche, were also used for comparison.
The mean age was 7.2 years for the 28 prepubertal girls (range, 4-12 years); 10.8 years for the 13 pubertal girls (range, 8-13 years); and 13.7 years for the early menarchal girls (range, 10-16 years). The girls had a mean body mass index (BMI) of 16 kg/m2, 23.5 kg/m2, and 22.8 kg/m2, respectively.
The mean antral follicle count was 15.9 in the prepubertal group, 21.5 in the pubertal group, and 20.4 in the early menarchal group, said Dr. Cooper of the division of reproductive endocrinology and infertility at Washington University in St. Louis.
One ovary was visualized on ultrasound in 94% of prepubertal girls and 86% of pubertal girls, and both ovaries were visualized in 71% and 57%. By comparison, a single ovary was visualized in 94% of girls with early menarche and two ovaries in 83%.
The mean AMH level was 2.97 ng/mL in the prepubertal group and 3.46 ng/mL in the pubertal group, vs. 3.74 ng/mL in the early menarchal girls.
Same-day AMH level was correlated with antral follicle count in all premenarchal girls, with a correlation coefficient, or r value, of 0.6, she said. The r value was 0.7 for the menarchal girls and 0.6 for reproductive-age women in the parent trial.
In multivariable regression analysis that controlled for BMI, hormonal contraception, and number of ovaries visualized, the AMH level was significantly associated with the antral follicle count (P value less than .001).
When asked by the audience whether the researchers controlled for variability that exists between sonographers, Dr. Cooper replied that the study used three dedicated sonographers and that intra- and intersonography correlation was very good when analyzed.
Another attendee questioned whether transabdominal antral follicle count data are transferable to data obtained with transvaginal scans.
Dr. Cooper replied, "I just don’t think we have enough data yet to say we can use transabdominal scans in these young girls, and that’s intentionally why I tried to correlate it with the same-day AMH measure to show that these measures are correlated," she said. "I think it is something that we can consider and further study."
An international group of specialist reproductive medicine clinicians and scientists recently convened to provide practical recommendations addressing the considerable variability that exists in the clinical definitions and technical methods used to count and measure antral follicles in research trials and clinical practice (Fertil. Steril. 2010;94:1044-51). In clinical practice, they recommend selecting patients with regular menstrual cycles, counting follicles between days 2 and 4 of a spontaneous menstrual or oral contraceptive cycle, and including all antral follicles 2-10 mm in diameter. It is suggested that a limited number of staff, adequately trained in transvaginal sonography, should perform antral follicle counts using real-time, two-dimensional imaging with a transvaginal transducer and a probe with a minimum frequency of 7 MHz.