Risk factors for poor oocyte yield and oocyte immaturity after GnRH agonist triggering.

STUDY QUESTION: What are the potential risk factors for poor oocyte recuperation rate (ORR) and oocyte immaturity after GnRH agonist (GnRHa) ovulation triggering? SUMMARY ANSWER: Lower ovarian reserve and LH levels after GnRHa triggering are risk factors of poor ORR. Higher BMI and anti-Müllerian hormone (AMH) levels are risk factors of poor oocyte maturation rate (OMR). WHAT IS KNOWN ALREADY: The use of GnRHa to trigger ovulation is increasing. However, some patients may have a suboptimal response after GnRHa triggering. This suboptimal response can refer to any negative endpoint, such as suboptimal oocyte recovery, oocyte immaturity, or empty follicle syndrome. For some authors, a suboptimal response to GnRHa triggering refers to a suboptimal LH and/or progesterone level following triggering. Several studies have investigated a combination of demographic, clinical, and endocrine characteristics at different stages of the treatment process that may affect the efficacy of the GnRHa trigger and thus be involved in a poor endocrine response or efficiency but no consensus exists. STUDY DESIGN, SIZE, DURATION: Bicentric retrospective cohort study between 2015 and 2021 (N = 1747). PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients aged 18-43 years who underwent controlled ovarian hyperstimulation and ovulation triggering by GnRHa alone (triptorelin 0.2 mg) for ICSI or oocyte cryopreservation were included. The ORR was defined as the ratio of the total number of retrieved oocytes to the number of follicles >12 mm on the day of triggering. The OMR was defined as the ratio of the number of mature oocytes to the number of retrieved oocytes. A logistic regression model with a backward selection method was used for the analysis of risk factors. Odds ratios (OR) are displayed with their two-sided 95% confidence interval. MAIN RESULTS AND THE ROLE OF CHANCE: In the multivariate analysis, initial antral follicular count and LH level 12-h post-triggering were negatively associated with poor ORR (i.e. below the 10th percentile) (OR: 0.61 [95% CI: 0.42-0.88]; P = 0.008 and OR: 0.86 [95% CI: 0.76-0.97]; P = 0.02, respectively). A nonlinear relationship was found between LH level 12-h post-triggering and poor ORR, but no LH threshold was found. A total of 25.3% of patients suffered from oocyte immaturity (i.e. OMR < 75%). In the multivariate analysis, BMI and AMH levels were negatively associated with an OMR < 75% (OR: 4.34 [95% CI: 1.96-9.6]; P < 0.001 and OR: 1.22 [95% CI: 1.03-1.12]; P = 0.015, respectively). Antigonadotrophic pretreatment decreased the risk of OMR < 75% compared to no pretreatment (OR: 0.72 [95% CI: 0.57-0.91]; P = 0.02). LIMITATIONS, REASONS FOR CAUTION: Our study is limited by its retrospective design and by the exclusion of patients who had hCG retriggers. However, this occurred in only six cycles. We were also not able to collect information on the duration of pretreatment and the duration of wash out period. WIDER IMPLICATIONS OF THE FINDINGS: In clinical practice, to avoid poor ORR, GnRHa trigger alone should not be considered in patients with higher BMI and/or low ovarian reserve, balanced by the risk of ovarian hyperstimulation syndrome. In the case of a low 12-h post-triggering LH level, practicians must be aware of the risk of poor ORR, and hCG retriggering could be considered. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Impact of Endometriosis Surgery on In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes: a Systematic Review and Meta-analysis.

Endometriosis-related infertility remains a therapeutic challenge. A burning issue in this field of research is determining whether pre-assisted reproductive technology (ART) surgery may be of some benefit in terms of reproductive outcomes. This systematic review and meta-analysis aimed at comparing ongoing pregnancy rates (OPR) and/or live birth rates (LBR) in patients who underwent endometriosis surgery before ART (IVF/ICSI) in comparison with patients who underwent first-line ART (IVF/ICSI). Searches were conducted from January 1990 to June 2021 on PubMed, Embase, and Cochrane Library using the following search terms: endometriosis, surgery, reproductive outcomes, and IVF/ICSI. The primary outcomes were OPR or LBR. A total of 19 studies were included in the meta-analysis. No statistically significant differences in LBR [0.91[0.63, 1.30]; I2 = 66%; n = 11], OPR [1.28[0.66, 2.49]; I2 = 60%; n = 3], and early pregnancy loss rate [0.88[0.62, 1.25]; I2 = 0%; n = 7] per cycle were found when comparing patients who underwent endometriosis surgery before IVF/ICSI and those who did not. After the exclusion of the studies with high risks of bias, the LBR per cycle was significantly reduced in the case of surgical treatment before IVF/ICSI [0.53[0.33, 0.86]; I2 = 30%; n = 4]. These data urge the clinician to carefully weigh the pros and cons before referring infertile patients with endometriosis to surgery before IVF, highlighting the key role of multidisciplinary referral centers.

The follicular output rate in normo-ovulating women undergoing ovarian stimulation is increased after unilateral oophorectomy.

STUDY QUESTION: Does unilateral oophorectomy modify the antral follicular responsiveness to exogenous FSH, assessed by the Follicular Output RaTe (FORT) in normo-ovulating women? SUMMARY ANSWER: Antral follicle responsiveness to exogenous FSH, as assessed by the FORT index, is significantly higher in women with a single ovary in comparison with the ipsilateral ovary of age-matched controls. WHAT IS KNOWN ALREADY: Growing evidence indicates that the innovative FORT may be a remarkable tool to evaluate the follicle responsiveness to exogenous FSH, independently of the size of the pretreatment cohort of small antral follicles. It is conceivable that in the unclear compensating mechanisms at play in women having undergone unilateral oophorectomy, an increase in the sensitivity of antral follicles to FSH may be involved. To clarify this issue, we decided to investigate whether the responsiveness of follicles to exogenous FSH, as assessed by the FORT, is altered in unilaterally oophorectomized patients. STUDY DESIGN, SIZE, DURATION: The study included 344 non-polycystic ovary syndrome, non-endometriotic women, aged 22-43 years old. There were 86 women who had a single ovary as a result of unilateral oophorectomy or adnexectomy (Single Ovary group; average time since surgery: 52 (8-156) months), and each of them was retrospectively matched with three patients having two intact ovaries, according to age (±1 year), year of ovarian stimulation, and FSH starting dose (±50 IU) (Control group, n = 258). PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum anti-Mullerian hormone (AMH) levels and total antral follicle count (AFC) (3-12 mm) were assessed on cycle day 3 in both groups. In all patients, follicles were counted before exogenous FSH administration (baseline) and on the day of oocyte trigger (OT) (dOT; preovulatory follicles; 16-22 mm). Antral follicle responsiveness to FSH was estimated in both groups by the FORT, determined by the ratio of the preovulatory follicle count on dOT × 100 to the small AFC at baseline. FORT in the Single Ovary group was compared to the overall FORT considering both ovaries or the index calculated on the ipsilateral ovary of matched controls. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, serum AMH levels and total AFC (1.0 (0.5-2.1) vs 1.8 (1.0-3.3), P < 0.005) and (9.0 (6.0-17.0) vs 13.0 (8.0-21.0), P < 0.001, respectively) were lower in the Single Ovary group compared to the Control group. When considering the FORT calculated on the basis of the overall ovarian response in women with two ovaries, the results were similar when compared to those obtained in patients unilaterally oophorectomized (30.4% (15.6-50.0) vs 32.5% (14.0-50.0), respectively). Interestingly, the comparison of FORT between women with a single ovary and the ipsilateral ovary of age-matched controls, revealed, after adjustment for AMH and AFC, a significantly higher ratio after unilateral oophorectomy (32.5% (14.8-50.0) vs 25.0% (10.0-50.0), P < 0.002, respectively). LIMITATIONS, REASONS FOR CAUTION: This study was based on retrospective data in a limited population. In addition, the FORT index has inherent limitations due to its indirect assessment of follicular responsiveness to FSH. WIDER IMPLICATIONS OF THE FINDINGS: The present investigation provides evidence that the responsiveness of antral follicles to exogenous FSH is increased in women having undergone unilateral oophorectomy when compared to the ipsilateral ovary of age-matched controls. This is consistent with the implication of a compensating phenomenon that drives the follicular changes in unilaterally oophorectomized patients. Further studies directly assessing the granulosa cell function and the density of FSH receptors in small antral follicles are required to confirm our findings. STUDY FUNDING/COMPETING INTEREST(S): The authors have no funding or competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

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.

[French clinical practice guidelines developed by a modified Delphi consensus process for oocyte vitrification in women with benign gynecologic disease]. / Indications de vitrification ovocytaire dans les pathologies gynécologiques bénignes : conseils de bonne pratique du CNGOF après étude de consensus par méthode Delphi.

OBJECTIVES: To provide clinical practice guidelines about fertility preservation (FP) for women with benign gynecologic disease (BGD) developed by a modified Delphi consensus process for oocyte vitrification in women with benign gynecologic disease. METHODS: A steering committee composed of 14 healthcare professionals and a patient representative with lived experience of endometriosis identified 42 potential practices related to FP for BGD. Then 114 key stakeholders including various healthcare professionals (n=108) and patient representatives (n=6) were asked to participate in a modified Delphi process via two online survey rounds from February to September 2020 and a final meeting. Due to the COVID-19 pandemic, this final meeting to reach consensus was held as a videoconference in November 2020. RESULTS: Survey response of stakeholders was 75 % (86/114) for round 1 and 87 % (75/86) for round 2. Consensus was reached for the recommendations for 28 items, that have been distributed into five general categories: (i) Information to provide to women of reproductive age with a BGD, (ii) Technical aspects of FP for BGD, (iii) Indications for FP in endometriosis, (iv) Indications for FP for non-endometriosis BGD, (v) Indications for FP after a fortuitous diagnosis of an idiopathic diminished ovarian reserve. CONCLUSION: These guidelines provide some practice advice to help health professionals better inform women about the possibilities of cryopreserving their oocytes prior to the management of a BGD that may affect their ovarian reserve and fertility. STUDY FUNDING/COMPETING INTEREST(S): The CNGOF (Collège National des Gynécologues Obstétriciens Français) funded the implementation of the Delphi process.

Impact of oxygen tension according to embryo stage of development: a prospective randomized study.

Human embryo culture under 2-8% O2 is recommended by ESHRE revised guidelines for good practices in IVF labs. Nevertheless, notably due to the higher costs of embryo culture under hypoxia, some laboratories perform embryo culture under atmospheric O2 tension (around 20%). Furthermore, recent meta-analyses concluded with low evidence to a superiority of hypoxia on IVF/ICSI outcomes. Interestingly, a study on mice embryos suggested that oxidative stress (OS) might only have an adverse impact on embryos at cleavage stage. Hence, we aimed to demonstrate for the first time in human embryos that OS has a negative impact only at cleavage stage and that sequential culture conditions (5% O2 from Day 0 to Day 2/3, then «conventional¼ conditions at 20% O2 until blastocyst stage) might be a valuable option for human embryo culture. 773 IVF/ICSI cycles were included in this randomized clinical trial from January 2016 to April 2018. At Day 0 (D0), patients were randomized using a 1:2 allocation ratio between group A (20% O2; n = 265) and group B (5% O2; n = 508). Extended culture (EC) was performed when ≥ 5 Day 2-good-quality-embryos were available (n = 88 in group A (20% O2)). In subgroup B, 195 EC cycles were randomized again at Day 2 (using 1:1 ratio) into groups B' (5% O2 until Day 6 (n = 101)) or C (switch to 20% O2 from Day 2 to Day 6 (n = 94). Fertilization rate, cleavage-stage quality Day 2-top-quality-embryo (D2-TQE), blastocyst quality (Day 5-top-quality-blastocyst (D5-TQB) and implantation rate (IR) were compared between groups A and B (= cleavage-stage analysis), or A(20% O2), B'(5% O2) and C(5%-to-20% O2). Overall, characteristics were similar between groups A and B. Significantly higher rates of early-cleaved embryos, top-quality and good-quality embryos on Day 2 were obtained in group B compared to group A (P < 0.05). This association between oxygen tension and embryo quality at D2 was confirmed using an adjusted model (P < 0.05). Regarding blastocyst quality, culture under 20% O2 from Day 0 to Day 6 (group A) resulted in significantly lower Day 5-TQB number and rates (P < 0.05) compared to both groups B' and C. Furthermore, blastocyst quality was statistically equivalent between groups B' and C (P = 0.45). At Day 6, TQB numbers and rates were also significantly higher in groups B' and C compared to group A (P < 0.05). These results were confirmed analyzing adjusted mean differences for number of Day 5 and Day 6 top quality embryos obtained in group A when compared to those respectively in groups B' and C (P < 0.05). No difference in clinical outcomes following blastocyst transfers was observed. These results would encourage to systematically culture embryos under hypoxia at least during early development stages, since OS might be detrimental exclusively before embryonic genome activation.

Could hormonal and follicular rearrangements explain timely menopause in unilaterally oophorectomized women?

STUDY QUESTION: Does unilateral oophorectomy modify the relationship between serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC)? SUMMARY ANSWER: No altered 'per-ovary' and 'per-follicle' AMH production and antral follicle distribution was evident in unilaterally oophorectomized women compared to matched controls. WHAT IS KNOWN ALREADY: The age of menopause onset is relatively unchanged in patients having undergone unilateral oophorectomy. Mechanisms that occur to preserve and maintain ovarian function in this context remain to be elucidated. STUDY DESIGN, SIZE, DURATION: Forty-one infertile women, with no polycystic ovary syndrome (PCOS) and no endometriosis, aged 19-42 years old, having undergone unilateral oophorectomy (One Ovary group; average time since surgery: 23.8 ± 2.2 months) were retrospectively age-matched (±1 year) with 205 infertile women having two intact ovaries and similar clinical features (Control group). PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum AMH levels, 3-4 mm AFC, 5-12 mm AFC, and total AFC (3-12 mm) were assessed on cycle Day 3 in both groups. Hormonal and ultrasonographic measurements obtained from patients in the Control group (i.e. having two ovaries) were divided by two to be compared with measurements obtained from patients of the One Ovary group (i.e. having one single remaining ovary). To estimate per-follicle AMH production, we calculated the ratio between serum AMH levels over 3-4 mm AFC, 5-12 mm AFC, and total AFC (3-12 mm), and the strength of the correlation between serum AMH levels and total AFC. The main outcome measure was to assess Day 3 AMH/Day 3 AFC ratio and hormonal-follicular correlation. MAIN RESULTS AND THE ROLE OF CHANCE: As expected, before correction, mean serum AMH levels (1.46 ± 0.2 vs 2.77 ± 0.1 ng/ml, P < 0.001) and total AFC (7.3 ± 0.6 vs 15.1 ± 0.4 follicles, P < 0.0001) were lower in the One Ovary group compared to the Control group, respectively. Yet, after correction, per-ovary AMH levels (1.46 ± 0.2 vs 1.39 ± 0.1 ng/ml) and total AFC (7.3 ± 0.6 vs 7.5 ± 0.2 follicles) values were comparable between the two groups. Consistently, per-follicle AMH levels (3-4 mm, 5-12 mm, and total) were not significantly different between the two groups (0.39 ± 0.05 vs 0.37 ± 0.02 ng/ml/follicle; 0.69 ± 0.12 vs 0.59 ± 0.05 ng/ml/follicle, and 0.23 ± 0.03 vs 0.19 ± 0.01 ng/ml/follicle; respectively). In addition, the prevalence of 3-4 mm follicles was comparable between the two groups (66.7% for One Ovary group vs 58.8% for Control group, respectively). Finally, the correlation between serum AMH levels and total AFC was similar for patients in the One Ovary group (r = 0.70; P < 0.0001) compared to those in the Control group (r = 0.68; P < 0.0001). LIMITATIONS/REASONS FOR CAUTION: The retrospective character of the analysis might lead to potential bias. WIDER IMPLICATIONS OF THE FINDINGS: The present investigation did not provide evidence of altered 'per-ovary' and 'per-follicle' AMH production and antral follicle distribution in unilaterally oophorectomized women compared to matched controls. Further studies are warranted to support the hypothesis that follicle-sparing mechanisms are clearly at stake in remaining ovaries after unilateral oophorectomy to explain their long-lasting function and timely menopausal onset. STUDY FUNDING/COMPETING INTEREST(S): The authors have no funding or competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Serum progesterone level and ongoing pregnancy rate following frozen-thawed embryo transfer after artificial endometrial preparation: a monocentric retrospective study.

INTRODUCTION: In some studies, early pregnancy loss (EPL) rate is higher with artificial cycle (AC) endometrial preparation for frozen-thawed embryo (FET) transfer than with other protocols, even though pregnancy rates are similar. An inadequate luteal phase support could explain these findings. The aim of this study was to compare, among the patients who had a pregnancy after FET with AC endometrial preparation, serum progesterone (PG) levels between those who experienced an EPL or an ongoing pregnancy. MATERIAL AND METHODS: A monocentric retrospective cohort study, conducted at a University affiliated fertility center, studied 130 FET cycles with AC endometrial preparation between June 2016 and July 2017. Serum PG rates were compared according to reproductive outcomes and to endometrial preparation protocol on day 10 or 12 after FET (PG0) according to the embryo stage, and every 48h in case of pregnancy (i.e. PG1; PG2). RESULTS: Among patients who had a pregnancy after FET with AC (n=33), serum PG levels were higher in case of an ongoing pregnancy than EPL, only significantly at PG1 (PG0 12.4ng/mL [7.5-14.6] vs 8.2ng/mL [6.0-13.0], p= 0.320; PG1 15.0 ng/mL [14.0-15.9] vs 8.5ng/mL [5.9-13.8], p= 0.048). DISCUSSION: We found that serum PG level was lower in women experiencing early pregnancy loss after FET with AC endometrial preparation, potentially reflecting a lack of appropriate luteal phase support with PG. A cycle AC test, monitoring serum PG levels after its steady state, could detect this lack of PG, allowing physicians to adapt PG supplementation.

[Progesterone and frozen-thawed embryo transfer after hormonal replacement therapy for endometrial preparation: An update on medical practices]. / Progestérone et transfert d'embryon congelé préparé par traitement hormonal substitutif : état des lieux des pratiques.

Frozen-thawed embryo transfer (FET) has recently become the most frequently performed ART procedure. Many protocols for endometrial preparation are used, without any evidence-based superiority of one protocol above the others. Most French fertility centers mainly use hormonal replacement treatment (HRT) for endometrial preparation for organizational reasons. According to some studies, early pregnancy losses rate is higher with HRT endometrial preparation for FET than with other protocols, leading to new insights in improving outcomes into ART centers. There is a lack of consensual guidelines regarding the use of HRT for FET: there are various protocols, with different dosages, duration and routes for progesterone (PG) prescription. To date, the vaginal route is the most popular around the world as it gives higher intra-uterine concentration of PG because of the first uterine pass. However, recent scientific publications have pointed the importance of PG measurement in order to detect a lack of PG supplementation. Whatever the route of administration, it seems that a significant proportion of patients do not reach adequate PG concentrations for successful implantation and ongoing pregnancy. Timing of the measurement and ideal serum PG rate to reach are yet to be defined. What treatment strategy to adopt according to the results is still under investigation. Individualization of PG doses and routes of administration could lead to a decrease in miscarriages and better outcome.

[Assisted reproductive technologies in HIV patients: Which results and which strategy in France in 2019?] / Prise en charge des couples porteurs du VIH en assistance médicale à la procréation : quels résultats et quelle stratégie en France en 2019 ?

With the use of antiretroviral therapy, HIV transmission from mother to fetus and between sexual partners has been significantly reduced, successively allowing pregnancy, then assisted reproductive technologies, and targeted unprotected sex among couples living with HIV. Since first French Morlat report in 2013, natural procreation is now possible under certain conditions for these couples living with HIV and the use of assisted reproductive technologies is increasingly limited to the treatment of infertility. While the results of intrauterine insemination seem satisfactory for serodiscordant couples living with HIV, in vitro fertilization results appear to be unfavorable when the woman is infected with HIV. In vitro fertilization results appear to be comparable to those in general population when only the man is infected with HIV. It can be assumed that ovaries are impacted by the treatment and/or the HIV in infected women.

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.

[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.

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.

[Impact of end-stage renal disease and kidney transplantation on the reproductive system]. / Impact de l'insuffisance rénale chronique et de la greffe rénale sur la fonction reproductive.

Chronic renal failure leads to many metabolic disorders affecting reproductive function. For men, hypergonadotropic hypogonadism, hyperprolactinemia, spermatic alterations, decreased libido and erectile dysfunction are described. Kidney transplantation improves sperm parameters and hormonal function within 2 years. But sperm alterations may persist with the use of immunosuppressive drugs. In women, hypothalamic-pituitary-ovarian axis dysfunction due to chronic renal failure results in menstrual irregularities, anovulation and infertility. After kidney transplantation, regular menstruations usually start 1 to 12 months after transplantation. Fertility can be restored but luteal insufficiency can persist. Moreover, 4 to 20% of women with renal transplantation suffer from premature ovarian failure syndrome. In some cases, assisted reproductive technologies can be required and imply risks of ovarian hyperstimulation syndrome and must be performed with caution. Pregnancy risks for mother, fetus and transplant are added to assisted reproductive technologies ones. Only 7 authors have described assisted reproductive technologies for patients with kidney transplantation. No cases of haemodialysis patients have been described yet. So, assisted reproductive technologies management requires a multidisciplinary approach with obstetrics, nephrology and reproductive medicine teams' agreement.

[Ovulation induction by pulsatile GnRH therapy in 2014: literature review and synthesis of current practice]. / 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.