The follicular output rate in normo-ovulating women undergoing ovarian stimulation is increased after unilateral oophorectomy.

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 < 0.005) and (9.0 (6.0-17.0) vs 13.0 (8.0-21.0), P < 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 < 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.

[1]  K. Rodriguez-Wallberg,et al.  Live birth and pregnancy rates after in vitro fertilization/intracytoplasmic sperm injection in women with previous unilateral oophorectomy: a systematic review and meta-analysis. , 2022, Fertility and sterility.

[2]  M. Peigné,et al.  Could hormonal and follicular rearrangements explain timely menopause in unilaterally oophorectomized women? , 2021, Human reproduction.

[3]  R. Vallone,et al.  Understanding Ovarian Hypo-Response to Exogenous Gonadotropin in Ovarian Stimulation and Its New Proposed Marker—The Follicle-To-Oocyte (FOI) Index , 2018, Front. Endocrinol..

[4]  A. Lass Is single ovary a detrimental factor for live-birth rate in IVF? , 2018, Human reproduction.

[5]  M. Eijkemans,et al.  Back to the basics of ovarian aging: a population-based study on longitudinal anti-Müllerian hormone decline , 2016, BMC Medicine.

[6]  A. Eskild,et al.  Is unilateral oophorectomy associated with age at menopause? A population study (the HUNT2 Survey). , 2014, Human reproduction.

[7]  E. Stewart,et al.  Unilateral oophorectomy results in compensatory follicular recruitment in the remaining ovary at time of ovarian stimulation for in vitro fertilization. , 2014, Fertility and sterility.

[8]  P. Ho,et al.  Ovarian sensitivity index is a better measure of ovarian responsiveness to gonadotrophin stimulation than the number of oocytes during in-vitro fertilization treatment , 2014, Journal of Assisted Reproduction and Genetics.

[9]  Zi-jiang Chen,et al.  Prediction of IVF/ICSI outcome based on the follicular output rate. , 2013, Reproductive biomedicine online.

[10]  Kunihiko Hayashi,et al.  Factors associated with premature ovarian failure, early menopause and earlier onset of menopause in Japanese women. , 2012, Maturitas.

[11]  N. Frydman,et al.  Antral follicle responsiveness to follicle-stimulating hormone administration assessed by the Follicular Output RaTe (FORT) may predict in vitro fertilization-embryo transfer outcome. , 2012, Human reproduction.

[12]  R. Fanchin,et al.  Serum anti-Müllerian hormone levels are negatively related to Follicular Output RaTe (FORT) in normo-cycling women undergoing controlled ovarian hyperstimulation. , 2011, Human reproduction.

[13]  S. Loh,et al.  Treatment outcome of women with a single ovary undergoing in vitro fertilisation cycles. , 2010, Singapore medical journal.

[14]  D. H. Mendez Lozano,et al.  Coordination of antral follicle growth: basis for innovative concepts of controlled ovarian hyperstimulation. , 2005, Seminars in reproductive medicine.

[15]  E. Alataş,et al.  The outcomes of assisted reproductive technology cycles in patients with one or two ovaries , 2003, The journal of obstetrics and gynaecology research.

[16]  K. Diedrich,et al.  Comparison of the response to ovarian stimulation between women with one ovary and those with two ovaries, in a program of ICSI/ET , 2003, Acta obstetricia et gynecologica Scandinavica.

[17]  E. Nieschlag,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2000 by The Endocrine Society Ovarian Response to Follicle-Stimulating Hormone (FSH) Stimulation Depends on the FSH Receptor Genotype* , 2022 .

[18]  A. Hsueh,et al.  Initial and cyclic recruitment of ovarian follicles. , 2000, Endocrine reviews.

[19]  J D Thomas,et al.  Tissue harmonic imaging: why does it work? , 1998, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[20]  M. Faddy,et al.  A mathematical model of follicle dynamics in the human ovary. , 1995, Human reproduction.

[21]  M. Faddy,et al.  Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. , 1992, Human reproduction.

[22]  G. Hodgen,et al.  Effects of ovarian tissue reduction on the menstrual cycle: persistent normalcy after near-total oophorectomy. , 1989, Biology of reproduction.