The serum level of anti-Mullerian hormone (AMH), a product from granulosa cells involved in follicle growth, has been shown to correlate tightly with the small antral follicle number (FN) at ultrasonography (U/S) in women who do not have polycystic ovary syndrome (PCOS). Because PCOS is associated with a 2- to 3-fold increase in growing FN, we investigated whether an increased AMH serum level correlates to other hormonal and/or U/S features of PCOS. Serum AMH has been assayed in 104 women (59 symptomatic PCOS, 45 controls) between d 2 and 7 after the last either spontaneous or progestin-induced (in PCOS) menstrual period. Mean serum AMH level was markedly increased in the PCOS group (47.1 +/- 22.9 vs. 20.8 +/- 11.6 pmol/liter in controls; P < 0.0001), an increase in the same order of magnitude as the one of the FN in the 2- to 5-mm range at U/S (12.8 +/- 8.3 vs. 4.8 +/- 1.9; P < 0.0001, respectively). The ratio AMH/FN was similar between the two groups (4.8 +/- 3.4 vs. 4.8 +/- 2.9; P = 0.55). By simple regression, both in PCOS and controls, the AMH level was positively related to the 2- to 5-mm FN at U/S (P < 0.0001 and P < 0.03, respectively), but not to the 6- to 9-mm FN, and was negatively correlated to the serum FSH level (P < 0.02 and P < 0.04, respectively). AMH was also positively related to the serum testosterone and androstenedione levels, in PCOS exclusively (P < 0.0005 and <0.002, respectively). No relationship was found between AMH and age, serum estradiol, inhibin B, and LH levels in both groups. After multiple regression only the 2- to 5-mm FN remained significantly related to AMH in PCOS whereas testosterone, androstenedione, and FSH were no longer. In conclusion, the assay of the serum AMH may represent an important breakthrough in the diagnosis and in the understanding of PCOS. Our data suggest that the increase of AMH serum level in PCOS is the consequence of the androgen-induced excess in small antral FN and that each follicle produces a normal amount of AMH. We hypothesize that an increased AMH tone within the cohort could be involved in the follicular arrest of PCOS, by interacting negatively with FSH at the time of selection.

Within GCs, the balance between FSH and AMH effects is pivotal in the shift from androgen- to oestrogen-driven follicles. Our two triangles hypothesis, based on updated data from the literature, offers a pedagogic template for the understanding of folliculogenesis in the normal and polycystic ovary. It opens new avenues for the treatment of anovulation due to PCOS.

We propose to modify the definition of polycystic ovaries by adding the presence of > or =12 follicles measuring 2-9 mm in diameter (mean of both ovaries). Also, our findings strengthen the hypothesis that the intra-ovarian hyperandrogenism promotes excessive early follicular growth and that further progression cannot proceed normally because of hyperinsulinism and/or other metabolic influence linked to obesity.

Susceptibility of the ovarian reserve to chemotherapy is highly variable from one patient to another and poorly documented. To better characterize the evolution of follicular depletion in patients treated for lymphoma, serum anti-Müllerian hormone (AMH) assay was used. A total of 30 young women (mean age 24years) were prospectively recruited before initiation of chemotherapy for lymphoma. They were assigned either to an adriamycin, bleomycin, vinblastine and dacarbazine protocol (ABVD group) or to a protocol that included cyclophosphamide (non-ABVD group). AMH assays were performed before and during chemotherapy, and then every 3months after the end of treatment for a period of 1year. In all patients, AMH concentrations fell drastically just after the start of chemotherapy and were close to the detection limit at the end of the treatment. In the ABVD group, AMH concentrations increased from the third month after the end of chemotherapy and returned to pretreatment values 12months after the end of chemotherapy. Conversely, no significant change was observed in the non-ABVD group throughout the follow-up period. In conclusion, longitudinal analysis of AMH during chemotherapy highlights differences between protocols that could contribute to an understanding of ovarian toxicity and, ultimately, be useful in fertility preservation counselling.

Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs.

The similarity of the first PC between controls and PCOS supports the hypothesis that the metabolic anomaly of PCOS is neither intrinsic nor specific. Conversely, by gathering the androgen and follicle variables, the second PC in PCOS may be viewed as summarizing a specific ovarian anomaly. Because both FN and/or serum AMH were strongly correlated to the second PC along with androgens, they may be used equally as surrogates for the classical markers of ovarian HA. This reconciles the Rotterdam Consensus and other definitions for PCOS, especially in women having the Rotterdam PCOS phenotype without HA. We thus propose a simple strategy for the diagnosis of PCOS in clinical practice.

A 5-day free interval after OCP or progestogen offers the advantages of gonadotrophin recovery and homogeneous follicular cohort, whereas early FSH rebound occurring after estrogen pre-treatment argues for a short free period.

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