Geoffroy Robin

Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries

BACKGROUND Polycystic ovarian morphology (PCOM) at ultrasound is currently used in the diagnosis of polycystic ovary syndrome (PCOS). We hypothesized that the previously proposed threshold value of 12 as an excessive number of follicles per ovary (FN) is no longer appropriate because of current technological developments. In this study, we have revisited the thresholds for FN and for the serum Anti-Müllerian hormone (AMH) level (a possible surrogate for FN) for the definition of PCOM. METHODS Clinical, hormonal and ultrasound data were consecutively recorded in 240 patients referred to our department between 2008 and 2010 for exploration of hyperandrogenism (HA), menstrual disorders and/or infertility. RESULTS According to only their symptoms, patients were grouped as: non-PCOS without HA and with ovulatory cycles (group 1, n = 105), presumption of PCOS with only HA or only oligo-anovulation (group 2, n = 73) and PCOS with HA and oligo-anovulation (group 3, n = 62). By cluster analysis using androgens, LH, FSH, AMH, FN and ovarian volume, group 1 appeared to be constituted of two homogeneous clusters, most likely a non-PCOM non-PCOS subgroup (n = 66) and a PCOM, non-PCOS (i.e. asymptomatic) subgroup (n = 39). Receiver operating characteristic curve analysis was applied to distinguish the non-PCOM non-PCO members of group 1 and to group 3. For FN and serum AMH respectively, the areas under the curve were 0.949 and 0.973 and the best compromise between sensitivity (81 and 92%) and specificity (92 and 97%) was obtained with a threshold values of 19 follicles and 35 pmol/l (5 ng/ml). CONCLUSIONS For the definition of PCOM, the former threshold of >12 for FN is no longer valid. A serum AMH >35 pmol/l (or >5 ng/ml) appears to be more sensitive and specific than a FN >19 and should be therefore included in the current diagnostic classifications for PCOS.

Role of Anti-Müllerian Hormone in pathophysiology, diagnosis and treatment of Polycystic Ovary Syndrome: a review

Polycystic ovary syndrome (PCOS) is the most common cause of chronic anovulation and hyperandrogenism in young women. Excessive ovarian production of Anti-Müllerian Hormone, secreted by growing follicles in excess, is now considered as an important feature of PCOS. The aim of this review is first to update the current knowledge about the role of AMH in the pathophysiology of PCOS. Then, this review will discuss the improvement that serum AMH assay brings in the diagnosis of PCOS. Last, this review will explain the utility of serum AMH assay in the management of infertility in women with PCOS and its utility as a marker of treatment efficiency on PCOS symptoms. It must be emphasized however that the lack of an international standard for the serum AMH assay, mainly because of technical issues, makes it difficult to define consensual thresholds, and thus impairs the widespread use of this new ovarian marker. Hopefully, this should soon improve.

Polycystic Ovary-Like Abnormalities (PCO-L) in Women with Functional Hypothalamic Amenorrhea

CONTEXT In the general population, about 30% of asymptomatic women have polycystic ovary-like abnormalities (PCO-L), i.e. polycystic ovarian morphology (PCOM) at ultrasound and/or increased anti-Müllerian hormone (AMH) serum level. PCOM has also been reported in 30-50% of women with functional hypothalamic amenorrhea (FHA). OBJECTIVE The aim of this study was to verify whether both PCOM and excessive AMH level indicate PCO-L in FHA and to elucidate its significance. DESIGN We conducted a retrospective analysis using a database and comparison with a control population. SETTING Subjects received ambulatory care in an academic hospital. PATIENTS Fifty-eight patients with FHA were compared to 217 control women with nonendocrine infertility and body mass index of less than 25 kg/m(2). INTERVENTIONS There were no interventions. MAIN OUTCOME MEASURES We measured serum testosterone, androstenedione, FSH, LH, AMH, and ovarian area values. The antral follicle count (AFC) was used as a binary variable (i.e. negative or positive) because of the evolution of its sensitivity over the time of this study. The ability of these variables (except AFC) to detect PCO-L in both populations was tested by cluster analysis. RESULTS One cluster (cluster 2) suggesting PCO-L was detected in the control population (n = 52; 24%), whereas two such clusters were observed in the FHA population (n = 22 and n = 6; 38 and 10%; clusters 2 and 3, respectively). Cluster 2 in FHA had similar features of PCO-L as cluster 2 in controls, with higher prevalence of positive AFC (70%) and PCOM (70%), higher values of ovarian area and higher serum AMH (P < 0.0001 for all), and testosterone levels (P < 0.01) than in cluster 1. Cluster 3 in FHA was peculiar, with frankly elevated AMH levels. In the whole population (controls + FHA), PCO-L was significantly associated with lower FSH values (P < 0.0001). CONCLUSION PCO-L in FHA is a frequent and usually incidental finding of unclear significance, as in controls. The association of PCO-L with hypothalamic amenorrhea should not lead to a mistaken diagnosis of PCOS.

Seminal plasma levels of anti-Müllerian hormone and inhibin B are not predictive of testicular sperm retrieval in nonobstructive azoospermia: a study of 139 men

OBJECTIVE To evaluate the seminal levels of the Sertoli anti-Müllerian hormone (AMH) and inhibin B in the testicular sperm extraction (TESE) in nonobstructive azoospermia. DESIGN Prospective study. SETTING Reproductive biology division in a university hospital. PATIENT(S) One hundred thirty-nine men. INTERVENTION(S) Men were classified on the basis of positive and negative TESE. MAIN OUTCOME MEASURE(S) Seminal levels of AMH and inhibin B, serum levels of FSH and inhibin B, testicular volume, sperm retrieval, and spermatogenesis. RESULT(S) The mean serum FSH and inhibin B concentrations were 21.4 IU/L and 54.68 pg/mL. Spermatozoa were retrieved in 43.17% of the men. Mean seminal AMH and inhibin B concentrations were 12.06±37.30 pmol/L and 142.72±950.91 pmol/L, respectively. Seminal AMH and inhibin B levels were simultaneously undetectable in 35.97% of subjects. Seminal plasma levels of AMH and inhibin B were positively correlated, as were seminal and serum inhibin B concentrations. The successful and failed TESE groups did not differ significantly in terms of either AMH or inhibin B seminal plasma concentrations. Combining the latter parameters with the serum FSH level did not improve the predictive value for successful TESE. The presence or absence of germ cells did not have a statistically significant relationship with seminal plasma AMH and inhibin B concentrations. CONCLUSION(S) There is no value in seminal plasma levels of AMH and inhibin B as criteria for sperm extraction in men with nonobstructive azoospermia.

Is polycystic ovarian morphology related to a poor oocyte quality after controlled ovarian hyperstimulation for intracytoplasmic sperm injection? Results from a prospective, comparative study

OBJECTIVE To evaluate the relationship between polycystic ovarian morphology (PCOM) and oocyte quality after controlled ovarian stimulation for intracytoplasmic sperm injection (ICSI). DESIGN Prospective, comparative study with concurrently treated and age-matched controls. SETTING Academic IVF unit of the Lille University Hospital. PATIENT(S) A total of 194 women were prospectively included before their first IVF-ICSI attempt for exclusive male infertility. They were classified into PCOM (n = 97) or control groups (n = 97) according to their follicle number per ovary. The nuclear maturation and morphologic aspects of 1,013 oocytes from PCOM patients were assessed and compared with those of 774 oocytes from controls. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Rate of metaphase II (MII) and morphologically abnormal oocytes. RESULT(S) The mean number of total and MII oocytes retrieved was significantly higher in the PCOM group. The rate of MII and morphologically abnormal oocytes was equivalent between the two groups. The mean number of embryos was significantly higher in the PCOM group. However, the percentage of top-quality embryos on day 3 was similar between the two groups. The implantation and clinical pregnancy rates were significantly higher in the PCOM group. CONCLUSION(S) Polycystic ovarian morphology does not have a negative impact on the quality of oocytes and embryos or the outcome of IVF-ICSI.

Cryptorchidie : de la physiopathologie à l’infertilité

Cryptorchidism is a defect of testicular descent. Hormonal, genetic and environmental factors might also contribute to the aetiology of cryptorchidism and its increased incidence in recent years in industrialised countries. Cryptorchidism itself might be considered a complex disease. This testicular pathology represents the best-characterized risk factor for reduced fertility and testicular cancer. The purpose of this review is to better understand physiopathology and mechanisms of infertility in men with history of cryptorchidism.

First intention IVF protocol for polycystic ovaries: does oral contraceptive pill pretreatment influence COH outcome?

BackgroundMorphological aspect of polycystic ovaries (PCO) is a very common finding in an IVF center population: this includes PCOS patients identified in 18–25% of the couples presenting with infertility and so called “sonographic PCO only” the prevalence of which has been estimated as high as 33% in asymptomatic patients. Finding the optimal first intention IVF protocol for polycystic ovaries patients is still challenging in order to improve the controlled ovarian hyperstimulation (COH) outcome while avoiding ovarian hyperstimulation syndrome (OHSS). It has been suggested that women with PCO would benefit from a longer period of pituitary down-regulation. The purpose of this study was to compare an extended duration of OCP pretreatment with a classic GnRH agonist protocol.MethodsA single center prospective non-randomized study was performed from January 2009 to December 2010 in the Lille University Hospital including 113 women diagnosed with PCO(S) according to the Rotterdam ultrasonographic criteria and undergoing their first IVF attempt. Comprehensive hormonal and ultra-sonographic assessments were collected during COH in these patients. LH and androgen suppression and dynamics of follicular growth were compared between the two protocols as well as the COH outcome in terms of oocyte/embryo number and quality, implantation and pregnancy rates.ResultsNo significant difference was observed between the two groups concerning dynamics of follicular growth and hormonal values. Clinical and ongoing pregnancy rates were significantly lower in the OCP group despite same oocyte and embryo quality. Nevertheless, the cumulative pregnancy rate did not differ between the two groups. The incidence of OHSS was not statistically significant.ConclusionsExtended duration of OCP pretreatment, as a first intention IVF protocol for PCO patients, does not improve the pattern of follicular growth nor the oocyte and embryo quality.

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.