Maëliss Peigné

Serum AMH level as a marker of acute and long-term effects of chemotherapy on the ovarian follicular content: a systematic review

Anti-Müllerian hormone (AMH) is a very sensitive indicator of the ovarian follicular content. Chemotherapeutic agents are notoriously ovariotoxic in that they damage follicles. The aim of this systematic review was to investigate the interest of serum AMH variations in determining the acute and long-term effects of chemotherapy on the ovarian reserve. According to the PRISMA guidelines, searches were conducted on PubMed for all English language articles until December 2013. Fifteen articles that focused on dynamic variations of AMH levels before and after chemotherapy were selected. Cancer patients have significantly lower AMH after chemotherapy than age-matched controls. Longitudinal studies of AMH variations before, during and after chemotherapy provide information about the degree of follicle loss for each patient according to different chemotherapy regimens. Different patterns of AMH levels during the ovarian recovery phase make it possible to discriminate between high and low gonadotoxic chemotherapy protocols. In addition, pretreatment AMH levels are shown to predict the long-term ovarian function after the end of treatment. These results may help to better understand the ovarian toxicity mechanisms of chemotherapy and to predict the degree of the ovarian follicle loss. Therefore, it can be useful for fertility preservation strategies, fertility counseling and future family planning.

Toward a better follow-up of ovarian recovery in young women after chemotherapy with a hypersensitive antimüllerian hormone assay

OBJECTIVE To evaluate the utility of a hypersensitive assay for measuring low antimüllerian hormone (AMH) levels in young cancer patients during the ovarian recovery phase of their chemotherapy. DESIGN Retrospective study. SETTING Academic medical center. PATIENT(S) Fifty-eight samples drawn at least 3 months after the end of chemotherapy in 30 women having either breast cancer (n=13) or hematologic malignancies (n=17) were selected to constitute two equally size groups: amenorrhea (n=30 samples) or spontaneous cycle (n=28 samples). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Serum AMH levels were measured by a conventional AMH ELISA (EIA AMH/MIS) and a hypersensitive ELISA (PicoAMH, AnshLabs) on the same sample. RESULT(S) Using a conventional assay, serum AMH was detectable (≥3 pmol/L) in 6.7% and in 10.7% of the samples corresponding to amenorrheic or cycling patients, respectively (nonsignificant). By contrast, with PicoAMH, serum AMH was detectable (≥0.07 pmol/L) in 71.4% of the samples from cycling women vs. 16.7% of the samples from amenorrheic patients. Multivariate regression analysis showed that among putative contributors, only the menstrual status (r=0.307) and serum FSH level (r=-0.546) were independently correlated to a detectable serum AMH with the picoAMH assay exclusively. CONCLUSION(S) The picoAMH assay, allowing measurement of very low AMH concentrations in human serum, should refine postchemotherapy ovarian follow-up in young women.

Pratiques et tendancesInduction de l’ovulation par administration pulsatile de GnRH en 2014 : revue de la littérature et synthèse des pratiques courantesOvulation induction by pulsatile GnRH therapy in 2014: Literature review and synthesis of current practice

The hypogonadotropic hypogonadism is an easily treatable form of female infertility. The most common cause of hypogonadotropic hypogonadism is functional hypothalamic amenorrhea. The GnRH pump is a simple and effective treatment to restore fertility of patients with hypothalamic amenorrhea: cumulative pregnancy rate is estimated between 70 and 100% after 6 cycles, compared to a low rate of complications and multiple pregnancies. While only 2.8 cycles are on average required to achieve a pregnancy with a pump, this induction of ovulation stays underused in France. The objective of this paper is to propose a practical manual of pulsatile GnRH, in order to improve the accessibility of pulsatile GnRH for patients with hypogonadotropic hypogonadism.

Induction de l’ovulation par administration pulsatile de GnRH en 2014 : revue de la littérature et synthèse des pratiques courantes

The hypogonadotropic hypogonadism is an easily treatable form of female infertility. The most common cause of hypogonadotropic hypogonadism is functional hypothalamic amenorrhea. The GnRH pump is a simple and effective treatment to restore fertility of patients with hypothalamic amenorrhea: cumulative pregnancy rate is estimated between 70 and 100% after 6 cycles, compared to a low rate of complications and multiple pregnancies. While only 2.8 cycles are on average required to achieve a pregnancy with a pump, this induction of ovulation stays underused in France. The objective of this paper is to propose a practical manual of pulsatile GnRH, in order to improve the accessibility of pulsatile GnRH for patients with hypogonadotropic hypogonadism.

Hyperandrogenism in women

Clinical signs of hyperandrogenism include hirsutism, acne and/or seborrhea, androgenic alopecia, menstrual disorders and at maximum virilization. Hirsutism is defined by the presence of a coarse and pigmented hair in male territory. In the Caucasian populations, a Ferriman Gallwey score ≥ 6 means hirsutism. Polycystic ovary syndrome is the most common cause of hyerandrogenism in women (70 % of cases) but must remain a diagnosis of exclusion. A neoplasm origin is suspected in case of recent onset of hyperandrogenism, which is rapidly progressive and with signs of virilization. The serum level of total testosterone and 17-hydroxyprogesterone and pelvic ultrasonography are the first line tests in case of clinical hyperandrogenism. Combined oral contraceptive pill can be the first line treatment in case of moderate hyperandrogenia, associated, if needed, with a specific acne treatment. Cyproterone acetate is the best-known and most effective antiandrogenic treatment. It decreases the hair density, speed of regrowth and pigmentation. It is indicated in severe hirsutism and must be combined with cosmetic cares.

Quintuplets after a transfer of two embryos following in vitro fertilization: a proved superfecundation

OBJECTIVE To report a genetically proved superfecundation of quintuplets after transfer of two embryos in IVF procedure and successful completion of the pregnancy after fetal reduction. DESIGN Case report. SETTING Academic reproductive medicine center. PATIENT(S) A 31-year-old woman, gravida 0, who underwent her second IVF cycle after three IUIs. INTERVENTION(S) After 5 years of primary infertility, three IUIs, and one IVF, the patient underwent her second IVF cycle with transfer of two fresh embryos on day 2. MAIN OUTCOME MEASURE(S) Development of five separate embryonic sacs. Fetal reduction to twins at 12 weeks of gestation. Successful pregnancy and delivery. Deoxyribonucleic acid analysis of the three reduced embryos, the live-born twins, and their parents. RESULT(S) Analysis of the seven DNA samples, because all were different, confirmed the superfecundation and disproved the zygotes division after transfer. Fetal growth restriction motivated preterm delivery by cesarean section. Both twins were in good health. CONCLUSION(S) Superfecundation can explain high-order multiple pregnancy and can be proved by DNA analysis. Couples must be informed because of the implications of fetal reduction for ethical issues, risks of pregnancy loss, fetal growth restriction, preterm delivery, and its consequences.

Is the suppressive effect of cyproterone acetate on serum anti-Müllerian-hormone levels in women with polycystic ovary syndrome stronger than under oral contraceptive pill?

Abstract Objective: To compare the suppressive effect of anti-androgen therapy by cyproterone acetate (CPA) and by oral contraceptive pill (OCP) on anti-müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) in order to detect a putative direct anti-androgen effect on AMH excess. Methods: This is a prospective longitudinal study including 58 women with PCOS between January 2010 and April 2014 at the Lille University Hospital. A total of 47 women with clinical hyperandrogenism were treated by CPA (50 mg/d was administered 20 days out of 28) and 11 women with PCOS but without clinical hyperandrogenism received OCP. Result(s): Serum AHM levels at baseline were similar in CPA and OCP groups (median [5–95th percentiles]: 60.4 pmol/l [25.1–200.2] versus 58 pmol/l [27.6–100], respectively, p = 0.39). After 3 months of treatment, serum AMH levels decreased significantly by 28% ± 20% and by 22% ± 27% in CPA and OCP groups, respectively. The decrease under both treatments was similar (p = 0.48). Conclusion(s): That any anti-androgen effect could be observed on AMH in our CPA group in addition to the gonadotropin-suppressing effect suggests that either androgens are not involved in AMH regulation or that they act by interfering with gonadotropin effects on granulosa cells.

The numbers of 2– 5 and 6–9 mm ovarian follicles are inversely correlated in both normal women and in polycystic ovary syndrome patients: what is the missing link?

STUDY QUESTION Is the negative correlation between the numbers of 2-5 and 6-9 mm follicles influenced by ovarian and/or metabolic parameter(s) in young control women and in patients with polycystic ovarian syndrome (PCOS)? SUMMARY ANSWER Our study confirmed that the negative correlation between numbers of follicles sized 2-5 and 6-9 mm was stronger in PCOS than in young control women and was not linked to any ovarian or metabolic parameter. WHAT IS KNOWN ALREADY Previous reports described a direct negative correlation between the number of small antral follicles (2-5 mm) and large antral follicle (6-9 mm) during the early follicular phase (cycle Days 2-5) in normal and PCOS women. Numerous factors, that could be either intrinsic to the ovary or secondary to metabolic influence and/or gonadotropin regulation, might account for this. STUDY DESIGN, SIZE, DURATION Six hundred and thirty-nine patients with PCOS according to Rotterdam Criteria and 157 control women were recruited in this retrospective cross-sectional study from January 2009 to January 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS Data were obtained from a database of clinical, hormonal and ultrasound (U/S) features recorded consecutively in a single reproductive medicine centre. Univariate correlations between the various parameters were analysed by the Spearmans correlation test. All variables significantly related to the 2-5 and/or 6-9 mm follicle numbers were included in a principal component analysis (PCA) in order to structure the data and to obtain collections of uncorrelated variables, called principal components (PC), which are linear combinations of the original variables. MAIN RESULTS AND THE ROLE OF CHANCE By univariate analysis, the 2-5 and 6-9 mm follicle numbers were strongly but negatively correlated in both populations. Many other variables were correlated to the 2-5 and/or 6-9 mm follicle numbers and to each other. By PCA, these relationships were gathered into four independent PCs in each population. In both groups, the 2-5 and 6-9 mm follicle numbers correlated strongly and inversely to a specific PC. Among the other variables tested, only serum oestradiol level correlated weakly to this PC in the control group. Two other uncorrelated PCs gathered relationships between variables linked to the metabolic status and the gonadotropin regulation both in control and PCOS women. Lastly, a fourth PC included relationships which linked to ovarian ageing in controls and to follicle dysregulation in patients with PCOS. LIMITATIONS, REASONS FOR CAUTION Our controls did not represent the general population since they were recruited in an ART centre; we used a modified Rotterdam classification for PCOS using follicle count and/or serum AMH level with in-house thresholds to define the follicle excess; the AMH assay used is no longer commercially available. WIDER IMPLICATIONS OF THE FINDINGS Factor(s) regulating specifically the equilibrium between the 2-5 and 6-9 mm follicle numbers still need(s) to be identified. More attention should be paid to the oocyte. STUDY FUNDING/COMPETING INTEREST(S) None.

L’hormone anti-müllérienne, témoin de l’ovario-toxicité de la chimiothérapie à court et long terme

Certaines chimiotherapies sont connues pour etre ovario-toxiques en portant atteinte au stock folliculaire de nos patientes. L’hormone anti-mullerienne (AMH) est un tres bon indicateur de ce stock folliculaire. L’objectif de cette revue a donc ete de recenser les travaux portant sur les variations du taux d’AMH avec la chimiotherapie pour essayer de determiner les effets a court et long terme de celle-ci sur la reserve ovarienne. Les recherches ont porte sur tous les articles en anglais publies dans PubMed jusqu’en juin 2013. Treize articles rapportant au moins un dosage d’AMH avant et apres chimiotherapie ont ete selectionnes pour analyse. Les patientes apres traitement d’un cancer ont significativement une AMH plus basse que les temoins de meme âge et plus basse que leur AMH avant le traitement. Les etudes longitudinales sur le taux d’AMH avant, pendant et apres chimiotherapie donnent des informations sur le degre de perte folliculaire par chaque patiente selon les differents protocoles de chimiotherapie. Des profils d’AMH differents pendant la phase de recuperation ovarienne permettent de discriminer entre les protocoles a faible ou a fort risque gonadotoxique. De plus, il a ete montre que le taux d’AMH avant traitement permet de predire la fonction ovarienne a long terme apres la fin du traitement. Ces resultats peuvent aider a mieux comprendre les mecanismes de toxicite ovarienne pendant la chimiotherapie et predire le degre de perte folliculaire. En pratique clinique, ils pourraient nous aider a mieux informer nos patientes sur leur fertilite apres chimiotherapie et sur les strategies possibles de preservation de la fertilite.

Endométriome décidualisé mimant une grossesse hétérotopique ovarienne

Mimant de nombreuses pathologies, la grossesse extra-uterine ovarienne (GEU) est de diagnostic difficile, surtout apres hyperstimulation ovarienne controlee et ponction ovocytaire en vue de fecondation in vitro (FIV). Nous rapportons ici le cas d’une femme de 28 ans adressee dans notre service pour suspicion de grossesse heterotopique ovarienne a la suite d’une FIV. Apres imagerie complementaire, le diagnostic a ete rectifie : l’image ovarienne correspondait a un endometriome decidualise. Habituellement pris pour une tumeur ovarienne maligne, l’endometriome decidualise est, pour la premiere fois, decrit ici comme un diagnostic differentiel rare de GEU ovarienne.