Pre-treatment AMH levels suggesting PCOM do not prevent chemotherapy-induced ovarian damage despite higher long-term ovarian reserve: a longitudinal study in 467 women treated with alkylating agents.

Authors

C Decanter, C Legrand, H Behal, A Mailliez, D Cavalieri, E D'Orazio, P Pigny

Published in

Human reproduction (Oxford, England). Aug 14, 2026. Epub Aug 14, 2026.

Abstract

Are young women with anti-Müllerian hormone (AMH) levels suggesting polycystic ovarian morphology (PCOM) at baseline better protected against chemo-induced ovarian damages?
Compared with women with lower baseline AMH levels, women with pre-treatment AMH levels suggesting PCOM experienced a similar degree of follicular loss and only partial recovery of baseline values after treatment but maintained significantly higher AMH levels at 12 and 24 months of follow-up and had a faster menstrual function resumption.
Longitudinal studies on AMH variations in women treated by chemotherapy have shown that pre-treatment AMH levels is one of the factors influencing the degree of the ovarian recovery. Recombinant AMH administration recently demonstrated a protective effect on ovarian follicles exposed to alkylating agents in mouse models. High AMH levels in women with polycystic ovaries have been associated with decreasing apoptosis of granulosa cells in small follicles and altered initial follicular growth.
This retrospective analysis of prospective collected data was carried out at the OncoFertility Observatory of the Lille University Hospital from January 2012 to February 2022. All women eligible for chemotherapy are prospectively recruited for ovarian function indicators follow-up until 24 months after the end of treatment.
467 women treated by alkylating agents for breast cancer (BC) or hematological malignancies (HM) were included in our Onco-Fertility Observatory and benefited from an onco-fertility consultation with discussion on fertility preservation options. The study population was divided into two groups according to basal AMH level at time of diagnosis: PCOM-like AMH levels ≥35 pmol/l before 2016 and ≥ 30 pmol/l after 2026 (PCOM group), and 8 ≥ AMH <35 pmol/l (non-PCOM group). Serial AMH measurements were performed at baseline before chemotherapy initiation (AMH0), 15 days after the start of chemotherapy (AMH1), 15 days before the last chemotherapy cycle (AMH2), and at time 3, 6, 12, 18, and 24 months from the end of chemotherapy. Menstrual function was assessed in parallel and antral follicle count (AFC) was performed at baseline, 12- and 24-month post-treatment. Serum AMH levels were measured using the second-generation enzyme immunoassay EIA AMH/MIS kit from 2012 to 2016, and by an automated AMH immunoassay on an Access Dxi analyzer thereafter. Results were secondarily homogenized using a validated conversion formula.
261 BC women aged 31.4 years, and 206 HM patients aged 24.4 years eligible for alkylating regimen were included before commencing treatment. Sixty-six women in the BC population were excluded from this study (death n = 4, recurrence n = 7, lost to follow-up n = 55) and 81 in the HM population (death n = 6, lost of follow-up n = 46, pregnancies n = 2, oophorectomy for cryopreservation n = 27). A total of 195 BC and 125 HM patients completed the whole follow-up and were finally analyzed. In BC group, women with PCOM were significantly younger (P = 0.002), had a higher incidence of menstrual disturbances at baseline (P = 0.003) and had more frequently a hormone receptor-positive (HR+) tumor (P = 0.04). In HM group, PCOM women were not significantly different from non-PCOM women concerning general characteristics. In BC and HM groups, pre-treatment AFC was significantly higher in PCOM group versus non-PCOM (37.8 ± 14.7 vs 17.3 ± 9.4; P ≤ 0.001 and 33.6 ± 12.4 vs 19.3 ± 8.4; P ≤ 0.001, respectively). In BC, as in HM population, a depletion phase can be distinguished from the beginning to the end of chemotherapy (AMH0-AMH2) and a recovery phase from the end of chemotherapy (AMH2) to the time +12 months followed by a sustaining phase between time +12 and 24 months. In BC as in HM population, before and after adjustment for the confounding variables (age, BMI, smoking and oral contraceptive (OC) use prior to chemotherapy), AMH values in the PCOM group remained significantly higher at time +12 and +24 months of follow-up. In BC PCOM subgroup, the AMH depletion slope was steeper and followed by a faster and higher AMH increase after the end of treatment, while no difference was observed between PCOM and non-PCOM HM women. In both cancer groups and in both subgroups of AMH levels, AMH values plateaued between Time +12 and Time +24 months (adjusted mean difference in log AMH (95% CI) 0.2 (-0.2 to 0.5) in BC population; 0.5 (-0.1 to 1.1) in HM population). At the end of follow-up, the frequency of undetectable AMH values in BC was 8.3% in PCOM versus 30.4% in non-PCOM (P = 0.0072) whereas, in HM group, there was no significant difference (18.7% vs 29.9%; P = 0.55). In HM, only three women, all from the PCOM group, recovered their pre-treatment values at the end of follow-up. In BC, none of the women recovered their initial AMH values. Clinically, the incidence of persistent amenorrhea at time +12months in HM subgroup tended to be lower in PCOM than in non-PCOM women but did not reach significance (13.3% vs 30.4%; P = 0.22). In BC subgroup, the incidence of persistent amenorrhea was significantly higher in non-PCOM women at time +12 months (2% vs 12%; P = 0.043) but no longer at time + 24 months.
the retrospective design of this study did not allow us to differentiate women with PCOS from women with PCOM only, as androgen levels were not routinely measured at baseline in this oncologic setting. The high incidence of women under OC at diagnosis (50%) may have underestimated the number of patients with AMH levels higher than 35 pmol/l. Two methods of AMH assays were used due to the long duration of the inclusion period but with validated and adapted cut-offs levels for the diagnosis of PCOM.
Fertility preservation and biological/clinical follow-up should be systematically offered to all women undergoing alkylating regimen, irrespective of their pre-treatment AMH level as very high ovarian follicular content does not preclude to significant follicle loss. A better understanding of the role of AMH in ovaries facing chemotherapy may ultimately help in developing ovarioprotective drugs.
This work was supported by Agence Régionale de Santé Hauts de France and Agence Onco Hauts-de-France who provided finances for AMH dosages (no. DOS/SDES/AR/FIR/2019/282).
No competing interests.
DC-2008-642 and CNIL DEC2015-112.

PMID:
42600055
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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