The follicular output rate in normo-ovulating women undergoing ovarian stimulation is increased after unilateral oophorectomy
Authors: Grynberg M , Pytel S , Peigne M , Sonigo C 
Published: March 2023

Abstract

STUDY QUESTION
Does unilateral oophorectomy modify the antral follicular responsiveness to exogenous FSH, assessed by the Follicular Output RaTe (FORT) in normo-ovulating women?

SUMMARY ANSWER
Antral follicle responsiveness to exogenous FSH, as assessed by the FORT index, is significantly higher in women with a single ovary in comparison with the ipsilateral ovary of age-matched controls.

WHAT IS KNOWN ALREADY
Growing evidence indicates that the innovative FORT may be a remarkable tool to evaluate the follicle responsiveness to exogenous FSH, independently of the size of the pretreatment cohort of small antral follicles. It is conceivable that in the unclear compensating mechanisms at play in women having undergone unilateral oophorectomy, an increase in the sensitivity of antral follicles to FSH may be involved. To clarify this issue, we decided to investigate whether the responsiveness of follicles to exogenous FSH, as assessed by the FORT, is altered in unilaterally oophorectomized patients.

STUDY DESIGN, SIZE, DURATION
The study included 344 non-polycystic ovary syndrome, non-endometriotic women, aged 22–43 years old. There were 86 women who had a single ovary as a result of unilateral oophorectomy or adnexectomy (Single Ovary group; average time since surgery: 52 (8–156) months), and each of them was retrospectively matched with three patients having two intact ovaries, according to age (±1 year), year of ovarian stimulation, and FSH starting dose (±50 IU) (Control group, n = 258).

PARTICIPANTS/MATERIALS, SETTING, METHODS
Serum anti-Mullerian hormone (AMH) levels and total antral follicle count (AFC) (3–12 mm) were assessed on cycle day 3 in both groups. In all patients, follicles were counted before exogenous FSH administration (baseline) and on the day of oocyte trigger (OT) (dOT; preovulatory follicles; 16–22 mm). Antral follicle responsiveness to FSH was estimated in both groups by the FORT, determined by the ratio of the preovulatory follicle count on dOT × 100 to the small AFC at baseline. FORT in the Single Ovary group was compared to the overall FORT considering both ovaries or the index calculated on the ipsilateral ovary of matched controls.

MAIN RESULTS AND THE ROLE OF CHANCE
Overall, serum AMH levels and total AFC (1.0 (0.5–2.1) vs 1.8 (1.0–3.3), P &lt; 0.005) and (9.0 (6.0–17.0) vs 13.0 (8.0–21.0), P &lt; 0.001, respectively) were lower in the Single Ovary group compared to the Control group. When considering the FORT calculated on the basis of the overall ovarian response in women with two ovaries, the results were similar when compared to those obtained in patients unilaterally oophorectomized (30.4% (15.6–50.0) vs 32.5% (14.0–50.0), respectively). Interestingly, the comparison of FORT between women with a single ovary and the ipsilateral ovary of age-matched controls, revealed, after adjustment for AMH and AFC, a significantly higher ratio after unilateral oophorectomy (32.5% (14.8–50.0) vs 25.0% (10.0–50.0), P &lt; 0.002, respectively).

LIMITATIONS, REASONS FOR CAUTION
This study was based on retrospective data in a limited population. In addition, the FORT index has inherent limitations due to its indirect assessment of follicular responsiveness to FSH.

WIDER IMPLICATIONS OF THE FINDINGS
The present investigation provides evidence that the responsiveness of antral follicles to exogenous FSH is increased in women having undergone unilateral oophorectomy when compared to the ipsilateral ovary of age-matched controls. This is consistent with the implication of a compensating phenomenon that drives the follicular changes in unilaterally oophorectomized patients. Further studies directly assessing the granulosa cell function and the density of FSH receptors in small antral follicles are required to confirm our findings.

STUDY FUNDING/COMPETING INTEREST(S)
The authors have no funding or competing interests to declare.

TRIAL REGISTRATION NUMBER
N/A.