Changes in circulating forms of anti-Muüllerian hormone and androgens in women with and without PCOS: a systematic longitudinal study throughout pregnancy.

STUDY QUESTION: What are the changes in serum concentration of total and cleaved anti-Muüllerian hormone (AMH) molecular forms and of androgens before and throughout pregnancy in women with and without polycystic ovary syndrome (PCOS) in a longitudinal follow-up investigation? SUMMARY ANSWER: Serum levels of total and cleaved AMH are higher from preconception to the third trimester of pregnancy in women with PCOS as compared to controls, whereas testosterone and androstenedione levels are higher in women with PCOS than in control women before pregnancy and during the second and third trimester of pregnancy. WHAT IS KNOWN ALREADY: Cross-sectional or partial longitudinal studies have shown higher AMH and androgen levels in pregnant women with PCOS as compared with non-PCOS women. To date, no complete longitudinal dynamic monitoring of the circulating forms of AMH and androgens from pre-conception to the third trimester of pregnancy have compared women with and without PCOS. STUDY DESIGN, SIZE, DURATION: This systematic prospective quarterly longitudinal monocentric study was a comparative follow-up of 30 women with PCOS and 29 controls before and during pregnancy from April 2019 to July 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18-43 years with a pre-conception measurement of AMH were included during the first trimester of a singleton pregnancy. The PCOS group was defined according to the Rotterdam diagnostic criteria. The control group patients included in the study had normal ovarian reserves. Circulating total and cleaved AMH, and serum estradiol, LH, and androgen levels were measured during the first, second, and third trimester of pregnancy in all study participants. MAIN RESULTS AND THE ROLE OF CHANCE: Before pregnancy, patients with PCOS had higher levels of AMH than controls. The total and cleaved AMH forms were significantly higher in women with PCOS than controls from pre-conception to the third trimester of pregnancy (all P < 0.001). Androgens (total testosterone and androstenedione) were higher in women with PCOS than controls from mid-pregnancy onwards. LIMITATIONS, REASONS FOR CAUTION: Our control population was a population of infertile women with no ovarian problems but most of them had undergone ART treatments to achieve pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: These results strengthen the hypothesis that gestational hyperandrogenism as well as exposure to elevated AMH levels in utero could be driving forces predisposing female progeny to develop PCOS. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by INSERM, France (grant number U1172) and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program, ERC-2016-CoG to P.G. grant agreement n° 725149/REPRODAMH. The authors have nothing to declare. TRIAL REGISTRATION NUMBER: NCT03483792.

[Spironolactone as a relay for cyproterone acetate in hyperandrogenic women]. / La spironolactone en relais de l'acétate de cyprotérone dans l'hyperandrogénie féminine.

OBJECTIVES: Cyproterone acetate is actually the first-line anti-androgenic treatment for severe hyperandrogenism in women. However, as this treatment is currently controversial, the objective of the study was to evaluate the safety and efficacy of spironolactone as a relay for cyproterone acetate. METHODS: This is a monocentric retrospective study conducted between December 2002 and January 2018 at the Jeanne de Flandre Hospital at the University Hospital Center of Lille. Patients with clinical hyperandrogenism who received treatment with cyproterone acetate and then spironolactone were included. A total of 37 patients were clinically and biologically evaluated before treatment, followed by cyproterone acetate and spironolactone. RESULTS: Clinically, the vast majority of patients were satisfied with the relay by spironolactone and found no difference between the two treatments. Biologically, testosterone and delta-4 androstenedione levels were significantly decreased with cyproterone acetate and spironolactone compared to no treatment. No significant differences were found when comparing levels under cyproterone acetate and under spironolactone. In addition, 87,5% of patients were free of side effects. CONCLUSIONS: The data collected show the clinical and biological efficacy of spironolactone as a relay for cyproterone acetate in the treatment of hyperandrogenism. This anti-androgen therefore appears as an effective and well-tolerated alternative, as a relay for cyproterone acetate in patients with hyperandrogenism.

Factors associated with pregnancy after in vitro fertilization in infertile patients with posterior deep pelvic endometriosis: A retrospective study.

INTRODUCTION: The management of posterior deep endometriosis is not consensual. This is due to a great heterogeneity of data from the literature. Many series were small and overall, predictors of pregnancy were not all included and analyzed by multivariate analysis. We conducted this study to evaluate the factors associated with pregnancy during the first two in vitro fertilization (IVF) attempts in infertile women with posterior deep endometriosis. MATERIAL AND METHODS: 230 women were included in this retrospective observational study, between January 1st, 2007 and September 30th, 2013, at the University Hospital of Lille. A large set of variables were recorded and their association with the chance of pregnancy was analyzed by multivariate analysis (MVA), including patients' features, endometriosis items, surgery procedures and IVF data. RESULTS: After 2 IVF attempts, 48.7% of the 230 women achieved a pregnancy, including 39.1% of ongoing pregnancies. Logistic regression analysis retained five variables significantly associated to the chance of pregnancy: oocyte retrieval number (OR=0.468 (0.296-0.739) p=0.001), age (OR=0.888 (0.811-0.974) p=0.011), single embryo transfer number (OR=1.494 (1.036-2.153) p=0.031), presence of a recto-uterine nodule (OR=0.454 (0.235-0.877) p=0.019) and IVF technique (OR=0.509 (0.272-0.951) p=0.034). CONCLUSION: The presence of a recto uterine nodule is associated with a lower chance of pregnancy after IVF. It has to be checked by prospective studies whether the finding of a recto-uterine nodule whose pejorative effect has not been reported so far should encourage to perform surgery before IVF in patients with deep endometriosis.

[Ovarian stimulation with gonadotrophins in patients with polycystic ovary syndrome]. / Stimulation ovarienne sous gonadotrophines chez des patientes atteintes de syndrome des ovaires polykystiques.

OBJECTIVES: The main objective of this study was to describe the ovulation rate in patients with polycystic ovary syndrome, treated with ovulation induction/intra-uterine insemination and follitropin alfa by gonadotrophins at a second attempt. METHODS: An observational, national and multicentre study was carried out: 51 French physicians (endocrinologists, gynaecologists) participated. Eligible patients were followed according to the usual clinical practices. The primary endpoint was the number of ovulations (spontaneous or triggered). Quality of life evaluation (by FertiQoL), compliance, and patient satisfaction were secondary endpoints. RESULTS: A total of 202 patients (mean age: 29.9 years; mean infertility: 2.9 years) were included: 78.4% met the Rotterdam definition. The ovulation rate was 93.3% (95% confidence interval [89.8; 96.8]%). At 12 weeks of gestation, 38 patients had an ongoing pregnancy. A difference of 10 points of the mean total FertiQoL score was observed between the two attempts. No patient reported missing injection. More than 9 in 10 patients said they were satisfied to very satisfied with the use of the pen injector for administration of follitropin alfa. Eight patients (4.0%) had hyperstimulation leading to cycle cancellation, and two patients (1.1%) reported ovarian hyperstimulation syndrome. CONCLUSIONS: At the second cycle of follitropin alfa stimulation, a high rate of ovulations, satisfactory compliance and tolerance profile associated with a change in quality of life were reported.

Recurrent maternal virilization during pregnancy in patients with PCOS: two clinical cases.

BACKGROUND: Maternal virilization during pregnancy is a rare phenomenon. Polycystic ovary syndrome (PCOS), luteoma and luteinic cysts are the most frequent and benign etiologies. This article presents two cases of recurrent maternal virilization during pregnancy. CLINICAL CASES: Our reported cases were young women with Afro-Caribbean and Nigerian origins. Data were collected by history-taking, clinical examination, laboratory investigations, transabdominal ultrasonographic examination and Magnetic Resonance Imaging. Both patients were diagnosed with PCOS according to the Rotterdam criteria. During each of their pregnancies they both developed an explosive hirsutism, a deepening in the voice, a clitoromegaly. Gestational diabetes occurred during pregnancies. There was no fetal virilization, despite raising androgen levels, more than tenfold to normal. Improvement of hirsutism and normalization of androgens were described in postpartum. CONCLUSION: Only few cases of maternal virilization during pregnancy were reported in literature and even fewer concern recurrent and bilateral ovarian etiology. Hyperplasia of ovarian theca cells seems to be the most likely explanation, which would suggest that PCOS belongs to a spectrum of abnormal reactivity of the ovary to human Chorionic Gonadotrophin (hCG) stimulation along with luteoma and luteinic cyst of pregnancy.  Insulin resistance could worsen hyperandrogenism but is not enough to explain virilization. Treatment should focus on protecting the fetus of possible virilization as well as its mother, but also on preserving the subsequent fertility in both.

Discordance between serum anti-Müllerian hormone concentrations and antral follicle counts: not only technical issues.

STUDY QUESTION: Do patient-specific features contribute to the differences between measured serum anti-Müllerian hormone (AMH) concentrations and AMH values expected from the corresponding antral follicle count (AFC)? SUMMARY ANSWER: Patient-specific features contribute to the differences between measured AMH values and AMH values expected from the corresponding AFC (AMHp), potentially through their effect on follicular AMH production. WHAT IS KNOWN ALREADY: Both patient counselling and patient management could be hampered by finding of disagreement between AFC and AMH if both are used for the prediction of ovarian response. The difference between measured AMH concentrations and AMH values expected according to the corresponding AFC cannot be entirely explained by the technical limitations of counting of antral follicles and analytical variability of the AMH assay used. STUDY DESIGN, SIZE, DURATION: This retrospective study analysed medical records of 1097 IVF patients collected between March 2011 and July 2013. PARTICIPANT/MATERIALS, SETTING, METHODS: The study population (N = 1097) included 705 (64.3%) women with normal ovarian morphology and 392 (35.7%) women with polycystic ovarian morphology, aged 20-44 years, who underwent their first IVF cycle in a single clinical centre. AMH was measured by a routine laboratory method and predicted AMH (AMHp) values were calculated using the linear regression equation (AMHp = -4.4 + 1.5 × AFC). The absolute value of the difference between AMH and AMHp was considered to be the measure of the degree of AMH-AFC agreement. The association of the difference between AMH and AMHp with clinical and biochemical parameters was investigated in both the higher-than-predicted (HTP) group comprising patients with AMH higher than AMHp (N = 466) and the lower-than-predicted (LTP) group comprising patients with AMH lower than AMHp (N = 631). MAIN RESULTS AND THE ROLE OF CHANCE: Patients in the HTP group had significantly longer menstrual cycle length and higher AMH and LH concentrations but lower AFC and FSH concentration than their counterparts in the LTP group. There was a significant association of absolute value of the difference between AMH and AMHp with age, menstrual cycle length, AFC, FSH and testosterone in both groups (P < 0.001). The difference between AMH and AMHp was exclusively correlated to LH in the HTP group (r = 0.159, P < 0.001) and to BMI in the LTP group (r = 0.231, P < 0.001), respectively. Multiple regression analysis revealed that only LH was significantly related to the difference between AMH and AMHp in the HTP group, independently from AFC. In the LTP group, BMI, menstrual cycle length, FSH and testosterone were found associated with the difference between AMH and AMHp, independently from AFC. LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study is selection bias. Data analysed in this study were collected from medical records of patients undergoing IVF treatment in a single department of human reproduction which precludes generalization of the results to women of different geographic origin, ethnicity, race and reproductive status. WIDER IMPLICATION OF THE FINDINGS: AMH higher than expected for a given AFC could suggest up-regulated AMH secretion (a typical feature of polycystic ovary syndrome) while AMH lower than expected from the corresponding AFC suggest down-regulated AMH secretion that could be seen as an early symptom of diminished ovarian reserve and premature ovarian insufficiency. In other words, when challenged against AFC, the serum AMH level is not only a quantitative but also a qualitative follicle marker, in relation with clinical and endocrine parameters. STUDY FUNDING/COMPETING INTEREST(S): No study funding was obtained for this study. The authors have no conflict of interest(s) to declare. TRIAL REGISTRATION NUMBER: Non-applicable.

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 Spearman's 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.

Counting ovarian antral follicles by ultrasound: a practical guide.

This Consensus Opinion summarizes the main aspects of several techniques for performing ovarian antral follicle count (AFC), proposes a standardized report and provides recommendations for future research. AFC should be performed using a transvaginal ultrasound (US) probe with frequency ≥ 7 MHz. For training, we suggest a minimum of 20-40 supervised examinations. The operator should be able to adjust the machine settings in order to achieve the best contrast between follicular fluid and ovarian stroma. AFC may be evaluated using real-time two-dimensional (2D) US, stored 2D-US cine-loops and stored three-dimensional (3D) US datasets. Real-time 2D-US has the advantage of permitting additional maneuvers to determine whether an anechoic structure is a follicle, but may require a longer scanning time, particularly when there is a large number of follicles, resulting in more discomfort to the patient. 2D-US cine-loops have the advantages of reduced scanning time and the possibility for other observers to perform the count. The 3D-US technique requires US machines with 3D capability and the operators to receive additional training for acquisition/analysis, but has the same advantages as cine-loop and also allows application of different imaging techniques, such as volume contrast imaging, inversion mode and semi-automated techniques such as sonography-based automated volume calculation. In this Consensus Opinion, we make certain recommendations based on the available evidence. However, there is no strong evidence that any one method is better than another; the operator should choose the best method for counting ovarian follicles based on availability of resources and on their own preference and skill. More studies evaluating how to improve the reliability of AFC should be encouraged. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

[How to deal with the different serum AMH kits in France in 2017?] / Les différentes trousses de dosage d'AMH en France en 2017 : comment s'y retrouver en pratique clinique quotidienne ?

Serum AMH measurement became a key element in clinical practice, especially before using Assisted reproductive techniques (ART). However, many AMH kits exist giving different AMH results, leading to a confusion in their interpretation. Until recently, only manual ELISA kits existed (mainly Gen II Beckman, EIA/AMH Immunotech and two Anshlab kits) reporting non-interchangeable results. High and low AMH cut-off values, mainly useful to adapt therapeutics in ART, were different between kits. Since the end of 2014, the arrival of two automatic assays (Access Dxi Beckman and AMH Elecsys Roche) seems to improve the sensitivity and the reproducibility of AMH measurement. It could simplify the interpretation of AMH values and improve our clinical choices. This review synthetizes the main comparisons between the different AMH kits available in 2017 to help clinicians in their daily clinical practice.

Polycystic ovarian morphology and the diagnosis of polycystic ovary syndrome: redefining threshold levels for follicle count and serum anti-Müllerian hormone using cluster analysis.

STUDY QUESTION: Can cluster analysis be used to differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with polycystic ovarian morphology (PCOM) in a non-subjective manner? SUMMARY ANSWER: Cluster analysis can be used to accurately and non-subjectively differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with PCOM. WHAT IS KNOWN ALREADY: Currently, PCOM is diagnosed using a fixed threshold level, i.e. 12 or more follicles per ovary, and is one of the diagnostic criteria of polycystic ovary syndrome (PCOS). However, PCOM is also encountered in normo-ovulatory women, suggesting that it could just represent a normal variant. On the other hand, recent studies have shown subtle endocrine abnormalities in women with isolated PCOM that resemble those found in women with PCOS. Because of the strong correlation between anti-Müllerian hormone (AMH) and follicle number, a high serum AMH level has been proposed as a surrogate marker for PCOM and could, therefore, be integrated in the diagnostic classifications for PCOS. STUDY DESIGN, SIZE, DURATION: This was a retrospective observational cohort study. Original cohorts had been recruited for previous studies between 1998 and 2010. Two hundred ninety-seven regularly cycling women and 700 women with PCOS were eligible for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cluster analysis was performed in 297 regularly cycling women. After exclusion of 'PCOM' clusters, each 'non-PCOM' cluster (young, n = 118 and old, n = 100) was included in the construction of a receiver operating characteristics curve to test the diagnostic performance of follicle number per ovary (FNPO) and serum AMH in discriminating similarly aged full-blown PCOS patients (n = 411 and 237, respectively) from normal regularly cycling non-PCOM women. MAIN RESULTS AND ROLE OF CHANCE: The optimal number of clusters was four; age was the most important classifying variable, followed by the FNPO and serum AMH. Two distinct clusters of normo-ovulatory women with PCOM were isolated and differed solely by age, i.e. 'young' and 'old'. Both 'PCOM' clusters had their similarly aged counterpart of 'non-PCOM' clusters. Likewise, two clusters comprised women younger than 30 years, with (n = 28, 'PCOM regularly cycling women') or without (n = 118, 'normal regularly cycling women') features of PCOM (increased FNPO and/or serum AMH). The two other clusters in older women could be labelled 'normal regularly cycling women' or 'PCOM regularly cycling women' (n = 100 and 51, respectively). The prevalence of PCOM was significantly greater in old than in young regularly cycling women controls. In the young population, after exclusion of the 'PCOM regularly cycling women', the diagnostic performance of AMH, expressed by area under the curve (AUC) (AUC = 0.903; CI (0.876-0.930)) to differentiate PCOS women from normal regularly cycling women was similar to that using the FNPO (AUC = 0.915, CI (0.891-0.940)) (P = 0.25), confirming results from earlier studies. In the old population, the diagnostic performance of AMH was greater than that of FNPO (AUCs = 0.948 (0.927-0.970) vs 0.874 (0.836-0.912), respectively, P = 0.00035). Cut-off levels of AMH and antral follicle count distinguishing regularly cycling non-PCOM women from PCOS women were higher in young women than in older women. LIMITATIONS, REASONS FOR CAUTION: Data of normal women were obtained from earlier studies, aiming to measure normal endocrine values. Apparently, the strong effect of age in cluster analysis revealed a dichotomy in the age distribution among the cohort of regularly cycling women included. This was involuntary since in none of the original studies, eligibility was limited by age and there was considerable overlap in age ranges of the cohorts. Transvaginal ultrasound was performed using a 6.5-8 mHz probe and our data confirm that this threshold level for FNPO is still valid if using such probe frequencies, although the use of devices with a maximum frequency lower than 8 mHz has become obsolete. Obviously, newer ultrasound scanner using higher transducer frequency will facilitate the detection of more follicles. WIDER IMPLICATIONS OF THE FINDINGS: Our data support the use of AMH as a surrogate for ultrasound to define PCOM, which is one of the three items of the Rotterdam classification. They also show that age should be taken into account to define the optimal threshold. The fact that the prevalence of PCOM was increased in the older regularly cycling women, may be due to 'attenuated' PCOS, a phenomenon that has been described in ageing women with PCOS. These women might have had anovulatory cycles in the past and have become ovulatory with increasing age, and were, therefore, eligible for this study. However, since most women included at older age have had spontaneous pregnancies in the past, PCOM at older age may be associated with a subclinical form of PCOS, which may also be present in young regularly cycling women. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. J.S.E.L. has received grants and support from Ferring, MSD, Organon, Merck-Serono, Schering Plough and Serono during recruitment and analysis of data for this study. S.L.F., A.D. and D.D. do not have any conflict of interest.

Could myo-inositol soft gel capsules outperform clomiphene in inducing ovulation? Results of a pilot study.

OBJECTIVE: Insulin resistance is known to worsen polycystic ovarian syndrome (PCOS). The management of insulin resistance is crucial in the treatment of PCOS and insulin-sensitizing molecule as myo-inositol (MYO) seems to have promising effects. The aim of our pilot study was to study whether supplementation with MYO can improve patients' sensitivity to clomiphene citrate (CC) in terms of ovulation and pregnancy rates. PATIENTS AND METHODS: This study included 26 patients with PCOS, eligible to ovulation induction with CC. All of them received MYO in combination with CC and folic acid, following the usual protocol. Results concerning ovulation and pregnancy rates were compared to those from our historical cohort of PCOS patients treated with CC alone. RESULTS: Ovulation rate was significantly higher with MYO+CC than with CC alone (65.5% vs. 42%, p=0.0001). The number of patients sensitive to 50 mg/d was 54% with MYO vs. 40% in our reference cohort (NS). The total resistance rate was 19% vs. 27% in the reference cohort (NS). Cumulative pregnancy rate with MYO+CC was 53.8% vs. 42.2% with CC alone (NS). Pregnancy rates per initiated cycle were 16.1% with MYO vs. 12.6% in the historical cohort (NS). DISCUSSION: Although the differences were not significant for most outcomes, probably due to the small number of patients, our pilot study seemed to show a benefit of supplementation with MYO during ovulation induction with CC in PCOS patients. CONCLUSIONS: This study proves the great interest of a RCT and re-opens the possibilities of insulin-sensitizing agents in the treatment of anovulatory patients with PCOS, such as natural products like MYO.

[Ovarian hyperstimulation syndrome after stimulation with highly purified hMGfor in vitro fertilization: Observational study SHOview]. / Le syndrome d'hyperstimulation ovarienne après stimulation par hMG hautement purifiée dans le cadre de la fécondation in vitro : étude observationnelle SHOview.

OBJECTIVE: Data on the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in France are limited. METHODS: Prospective observational multicentric study (23 French centers of IVF) in a cohort of 421 women treated with highly purified hMG (HP-hMG) for the first or second cycle of IVF with or without ICSI. The primary objective was to assess the incidence of moderate to severe OHSS in this cohort. RESULTS: At inclusion, 172 patients (40.9%) were considered at risk of OHSS by the physicians. The main measures for risk minimization taken by the physicians rested on initial dose of HP-hMG and protocol choice. At the end of the follow-up (4 months in average), the rate of OHSS moderate to severe was 2.4% (confidence interval 95%: 1.1-4.3%) for the studied IVF cycle. OHSS was severe for 3 women (0.7%) and moderate for 7 women (1.7%). CONCLUSION: This rate of OHSS after IVF is at the lower limit of the rates reported in the literature for OHSS. This study brings reassuring epidemiological data on the rate of OHSS in women at risk. The measures taken by the physicians to minimize the risk of OHSS could have contributed to this low incidence.

Extreme spermatogenesis failure: andrological phenotype and intracytoplasmic sperm injection outcomes.

Patients with very low sperm count through direct sperm examination can exhibit extreme oligozoospermia or cryptozoospermia (after centrifugation). The management of these patients is a real challenge for both clinicians and biologists. In this retrospective and comparative cohort study, we compared the andrological phenotype of patients with extreme alterations of spermatogenesis and assessed whether the origin of spermatozoa (testicular or ejaculate) had any influence on intracytoplasmic sperm injection (ICSI) outcomes. A total of 161 ICSI cycles were performed using ejaculated spermatozoa from 75 patients with extreme oligozoospermia (EOS) or cryptozoospermia (CS) and 150 ICSI cycles using extracted testicular spermatozoa from 74 patients with non-obstructive azoospermia (NOA). Physical, hormonal, ultrasound assessments, and ICSI outcomes were performed in each group. Cryptorchidism was significantly more frequent in the NOA group (60.8% vs. 22.6%, p = 0.001). FSH levels were significantly higher [18.9 IU/L (5.9-27.0) vs. 15.3 IU/L (9.0-46.5), p = 0.001] and the majority of inhibin B levels measured were found mostly undetectable in the NOA group as compared to EOS/CS group (31.1% vs. 10.7%, p = 0.0004). Moreover, we found no significant differences in the respect to the fertilization rates (48.9% and 43.3%, p = 0.43), implantation rates (17.4% and 15.9%, p = 0.77), and percentage of top quality embryo (22.4% and 20.4%, p = 0.73) between the two groups. The clinical pregnancy rates per embryo transferred were comparable in both groups (28.3% and 27.4%, p = 0.89). In this study, we showed for the first time a different andrological phenotype between EOS/CS and NOA groups. Indeed, cryptorchidism was significantly more frequent with more severe endocrine parameters found in the NOA group. These results reflect a more profound alteration in spermatogenesis in NOA patients. However, there was no difference in ICSI outcomes between NOA and EOS/CS groups.

Pregnancy after intracytoplasmic sperm injection following extended sperm preparation and hormone therapy in an azoospermic man with maturation arrest and microlithiasis: a case report and literature review.

In the management of azoospermia, a combination of testicular sperm extraction and intracytoplasmic sperm injection (ICSI) is usually the most successful option for fatherhood. However, an outstanding question remains: How can at least a few spermatozoa be obtained from the ejaculate, thus avoiding the need for a surgical procedure? A 36-year-old man presented to Assisted Reproduction Unit with his 26-year-old wife. The ultrasound assessment revealed bilateral microlithiasis. Two spermograms revealed absolute azoospermia. Levels of follicle-stimulating hormone (FSH) and luteinising hormone were normal-low. The patient underwent 10 months of treatment with clomiphene citrate. A bilateral testicular sperm extraction failed to retrieve spermatozoa and revealed a maturation arrest at spermatocyte/spermatid stages depending on the tubules. Clomiphene citrate was replaced with recombinant FSH (rFSH). After 9-month treatment with rFSH, motile spermatozoa from droplets of ejaculate pellet were cryopreserved as a single straw. Ovarian stimulation was provided using classic antagonist protocol, and five mature oocytes were collected. Two consecutive fresh semen samples on the day of ICSI yielded seven motile spermatozoa, and fertilisation was achieved in all five oocytes. On day 3, two embryos were transferred, yielding positive beta-human chorionic gonadotropin and a healthy delivery of a boy and a girl.

[Stimulation of spermatogenesis: For whom? Why? How?]. / Stimulation de la spermatogenèse : pour qui ? Pourquoi ? Comment ?

The stimulation of spermatogenesis is the best treatment of infertility for male hypogonadotropic-hypogonadism. The results are very pleasing because a real improvement of semen is sometimes obtained with spontaneous pregnants describing in the literature but after a long duration of treatment, often many months. Sometimes, the treatment improves the technical conditions of ICSI for the embryologists. Stimulation of spermatogenesis by gonadotrophins rFSH and/or hCG is the most used but others treatments, like pulsatile GnRH therapy or clomifene citrate can be used. The purpose of this review is to described the different protocols of stimulation of spermatogenesis and explain their results and finally to see if others indications of stimulation of spermatogenesis are existing.

[Infertility: A key time to follow a medical nutritional management. Our experience on 78 patients]. / Infertilité : moment clé pour entreprendre une prise en charge nutritionnelle médicale. Expérience lilloise sur 78 patientes.

OBJECTIVES: The prevalence of female obesity is increasing. Obesity leads to increased infertility and difficulties in the management of Assisted Reproductive Technology (ART). A specialized nutritional consultation was created in 2008 at University Hospital of Lille, to support infertile obese and overweight patients and to achieve a BMI below 35kg/m(2) before pregnancy. The aim of this retrospective study was to evaluate our practice of nutritional support on weight and pregnancy rate. METHODS: Seventy-eight obese or overweight patients, followed in nutrition and ART for at least two years, were compared to a control group of 119 normal weight patients. The nutritional strategy was mainly based on lifestyle changes, to establish healthier food and higher physical activity. RESULTS: The mean initial BMI was 37.5kg/m(2) vs 35.6kg/m(2) after nutritional support (significant weight loss, [P<0.001]). Obese or overweight patients had more frequently metabolic syndrome (P<0.01). The chances of pregnancy, after weight loss, were similar to the control group both in IUI and IVF/ICSI. However, gonadotropin doses were increased in the obese and overweight group (P=0.007). The hypocaloric diet was the most effective nutritional strategy to achieve a weight loss greater than 5% of initial weight (P=0.017). Regular physical activity practice allowed also more frequently to achieve this goal (P=0.074). Even after weight loss, a significant number of gestational diabetes (25% of pregnancies in our population) occurred in the obese or overweight group. CONCLUSION: This nutritional consultation promotes weight loss in infertile obese or overweight patients. The maternity desire is a strong motivational lever to weight loss, which leads to satisfying pregnancy rate.

[Does the serum AMH assay allow predicting reliably female fertility?]. / Le dosage de l'AMH permet-il de prédire de façon fiable la fertilité féminine ?

In women, the anti-Müllerian hormone (AMH) is secreted by the granulosa cells of growing follicles. Its measurement is strongly correlated with antral follicle count and represents a reliable marker of ovarian reserve. It also has the advantage of being highly reproducible since it has little variation within and between cycles. However, although it seems to be a good quantitative reflection of the ovarian reserve, it does not assess the oocyte quality. This drawback precludes any good prediction of female fertility in the general population. However, the AMH assay can become an indirect marker of female fertility in some situations at risk for premature ovarian failure or in the polycystic ovary syndrome. Its interest is no more to be proven in assisted reproductive technology where it is a valuable aid to the choice of the proposed techniques, ovarian stimulation protocols and gonadotropin doses. AMH is finally very informative in monitoring cancer patients having received ovariotoxic drugs or having undergone mutilating ovarian surgeries. In conclusion, although it cannot be considered itself as a reliable predictor of pregnancy in women, AMH is now a must in the management and treatment of female infertility.

The phenotypic diversity in per-follicle anti-Müllerian hormone production in polycystic ovary syndrome.

STUDY QUESTION: Is intrinsic dysregulation of granulosa cells (GC) and consequent increases in the per-follicle production of anti-Müllerian hormone (AMH), correlated with the phenotypic presentation of women with polycystic ovaries? SUMMARY ANSWER: Involvement of intrinsic GC dysregulation in oligo-anovulation associated with polycystic ovary syndrome (PCOS) is likely because among women with PCOS, those with oligo-amenorrhea have higher per-follicle AMH production than those who ovulate normally, irrespective of their androgen and/or metabolic status. WHAT IS KNOWN ALREADY: Women with PCOS have higher serum AMH level than non-PCOS women due to an increased follicle number and excessive AMH production per follicle, the latter reflecting a putative GC dysfunction that may vary between PCOS phenotypes. STUDY DESIGN, SIZE, DURATION: This is a retrospective analysis of data collected from 1021 women undergoing infertility evaluation from March 2011 to October 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women with polycystic ovarian morphology (PCOM) who met the Rotterdam criteria for PCOS (n = 272), women with PCOM only (n = 168) and controls (n = 581). MAIN RESULTS AND THE ROLE OF CHANCE: We used serum AMH to antral follicle count (AFC) ratio (AMH/AFC) as a marker of per-follicle AMH production and checked whether this ratio was associated with the PCOS phenotype and to the menstrual, androgen and metabolic status in women with PCOS, women with PCOM only and in controls. AMH/AFC was significantly higher in oligo-amenorrheic women with PCOS than in eumenorrheic women with PCOS or PCOM (P < 0.001) but also in the latter group compared with controls (P < 0.001) regardless of androgen status. Stepwise discriminant analysis yielded a significant score for the menstrual status with a discriminant power of 26.5% (P < 0.001). This score included AFC, AMH/AFC, waist circumference and LH with partial R(2) of 0.172, 0.042, 0.024 and 0.023, respectively. LIMITATIONS, REASONS FOR CAUTION: The AMH to AFC ratio as a surrogate marker for average AMH may be subject to error because follicles below the sensitivity limit of the ultrasonography used may also contribute to serum AMH concentration and secondly, AFC can be subjective. WIDER IMPLICATIONS OF THE FINDINGS: The higher AMH/AFC in women with PCOM only than in controls suggests that isolated PCOM may represent a PCOS-like phenotype in which an inherent dysfunction of GC exists but is too mild to affect the ovulatory process. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained for this study. There are no conflicts of interest to be declared. TRIAL REGISTRATION NUMBER: Non-applicable.

[Surgery for deep infiltrating endometriosis before in vitro fertilization: no benefit for fertility?]. / Chirurgie pour endométriose pelvienne profonde avant fécondation in vitro : pas de bénéfice pour la fertilité ?

OBJECTIVE: Does surgery for deep infiltrating endometriosis (DIE) before in vitro fertilization (IVF) improve pregnancy and birth rate? PATIENTS AND METHODS: Cohort study of 177 consecutive patients with DIE related infertility and receiving IVF. Patients were divided into 3 groups according to surgical management decided during multidisciplinary team meeting. Group no surgery (NS) (n=65), group complete surgery (CS) with complete resection of all lesions (n=49) and group incomplete surgery (IS) with gestures improving ovaries accessibility for IVF and/or facilitating embryonic implantation (n=63). Pre-surgery clinical, MRI lesion locations, and history of IVF characteristics were analyzed with logistic regression. RESULTS: There was no significant difference in general and IVF characteristics and in the severity of endometriosis among the three groups (P=0.43). Overall pregnancy and birth rates after IVF were 45.8% and 33.3%, respectively and were not different among the 3 groups (P=0.59 and P=0.49). Four major complications during oocytes retrievals were observed in NS group, one in IS group and none in CS group. Presence of an inter-utero-rectal lesion at MRI decreased the rate of pregnancy (OR=0.49 [0.25, 0.97]). DISCUSSION AND CONCLUSIONS: Surgery for deep infiltrating endometriosis does not improve pregnancy and birth rates before IVF. This inter-utero-rectal extensive lesion might explain IVF failures by ovarian difficult access and difficulties in embryonic transfers. Further studies should explore the impact of surgical excision of inter-utero-rectal lesion on oocyte retrieval and embryonic transfer.