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.

[Interest of iDAScore (intelligent Data Analysis Score) for embryo selection in routine IVF laboratory practice: Results of a preliminary study]. / Intérêt de l'iDAScore (intelligent Data Analysis Score) dans la pratique quotidienne d'un laboratoire de FIV pour la sélection embryonnaire : résultats d'une étude préliminaire.

INTRODUCTION: Embryo selection is a major challenge in ART, especially since the generalization of single embryo transfer, and its optimization could lead to the improvement of clinical results in IVF. Recently, several Artificial Intelligence (AI) models, based on deep-learning such as iDAScore, have been developed. These models, trained on time-lapse videos of embryos with known implantation data, can predict the probability of pregnancy for a given embryo, allowing automatization and standardization in embryo selection. MATERIAL AND METHODS: In this study, we have compared the hierarchical categorization of 311 D5 blastocysts of iDAScore v1.0 and the embryologists of our unit. These 311 D5 blastocysts have been classified as top (70.1%), good (Q+: 10.6%) and poor (Q-: 19.3%) quality by embryologists according to Gardner classification. Median iDAScores were [9.9-8.4],]8.4-7.5] and]7.5-2.1] for top, good and poor-quality blastocysts respectively. RESULTS: We observed a significantly concordant categorization between iDAScore and embryologists for top, good and poor-quality blastocysts (respectively, 89.5, 36.4 and 48.3%, P < 10-4). Moreover, the hierarchical categorization of the three best blastocysts between iDAScore and the embryologists was as follow: 1st rank: 71.9%; 2nd rank: 61.6%; 3rd rank: 56.8% (P=0.07). One hundred and fifty-one blastocysts with known implantation data were analyzed. The iDAScore of blastocysts that implanted was significantly higher than those that did not implant (implantation+: 9.10±0.57; implantation-: 8.70±0.95, P=0.003). CONCLUSION: This preliminary study shows that iDAScore is able to perform a reproducible, reliable and immediate hierarchical classification of blastocysts. Moreover, this tool can identify the blastocysts with the highest implantation potential. If these results confirmed on a larger scale of embryos and patients, IA could revolutionize IVF laboratories by standardizing embryo hierarchical selection.

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.

[Impact of the type of incubator (non-humidified versus humidified) on embryo culture media osmolality]. / Impact du type d'incubateur (atmosphère humidifiée versus sec) sur l'osmolalité des milieux de culture embryonnaire.

INTRODUCTION: Benchtop incubators with small individual chambers have been developed in order to improve the stability of embryo culture conditions reducing the environmental stress during the embryo development. These new dry incubators were designed without any air humidification system in order to prevent bacterial proliferation and to enable the use of time-lapse system. However, an elevated evaporation of the culture media could occur in these conditions. The main objective of the study is to analyse the impact of the used incubator type on the embryo culture media osmolality. MATERIALS AND METHODS: Microdrops of 50µL of culture media were placed in 60mm diameter culture dishes, and quickly covered with either 7 or 8mL of mineral oil in an IVF workstation with laminar airflow. Two series of culture dishes have been randomly placed either in a humidified incubator or in a dry benchtop incubator. The microdrops of each culture dishes were sampled at D0, D1, D2, D3, and D5 respectively to measure the osmolality in triplicate using a cryoscopic osmometer. The mean values of osmolality in each incubator have been compared respectively on D0, D1, D2, D3 and D5 with appropriate statistical tests, and considered statistically significant when P<0.05. RESULTS: The osmolality of the microdrops placed in the dry benchtop incubator differed significantly after the third day of culture, regardless of the level of mineral oil in the culture dishes. Indeed, using Petri dishes covered respectively with 7 or 8mL of mineral oil, osmolality values of samples from the dry incubator were significantly higher than those from the humidified one, at D3 and D5 (D3/7mL: 273±2.1 vs. 268±1.0mOsm/kg; P=0.02; D3/8mL: 282±8.0 vs. 270±0.7mOsm/kg; P=0.04) and D5 (D5/7mL: 283±1.5 vs. 270±3.6mOsm/kg; P=0.004; D5/8mL: 287±5.6 vs. 268±2.3mOsm/kg; P=0.005). Furthermore, the analysis on paired samples showed that the osmolality in the dry benchtop incubator at D5 using 7mL of oil (283±1.5mOsm/kg; P=0.003) and at D3 (273±2.1mOsm/kg; P=0.016) and D5 (287±5.6mOsm/kg; P=0.009) using 8mL of oil was significantly higher than that measured at D0 (265±1.9mOsm/kg). CONCLUSION: A significant increase of the embryo culture media osmolality was observed in the dry benchtop incubator with ambient hygrometry in our standard conditions. Adding 1mL of oil was not sufficient to reduce the evaporation of the media. Although maintained at a physiological level, the impact of the osmolality changes on the in vitro embryo development has to be further determined.

[Prospective comparison of different techniques for cryopreservation of small numbers of human spermatozoa]. / Étude prospective comparant plusieurs techniques de congélation de faibles nombres de spermatozoïdes humains.

OBJECTIVES: This study aimed to determine if vitrification is more efficient than the slow freezing method when cryopreservation of small numbers of human spermatozoa is needed and, if so, which device is the most suitable. METHODS: This is a prospective experimental study conducted in a university-affiliated assisted reproductive center. Ejaculates were obtained from the same fertile man after written consent. Selected sperm were cryopreserved by slow freezing method or vitrified in two different devices: Cell Sleeper and Stripper tip. RESULTS: Vitrification in Cell Sleeper provided significantly higher recovery, motility and survival rates than slow freezing. Only recovery rate was higher in Cell Sleeper than when using Stripper tip. Moreover, recovery time per spermatozoon was faster in Cell Sleeper than in the two other groups. Furthermore, statistical significance was achieved when comparing the four above parameters between Stripper tip and slow freezing, concluding to the superiority of vitrification in Stripper tip as well. Finally, the theorical time needed per injected oocyte was significantly shorter after vitrification in the two devices than when using slow freezing, and shorter in Cell Sleeper in comparison with Stripper tip. CONCLUSIONS: Vitrification, in particular using Cell Sleeper, appears as the most suitable method to cryopreserve small numbers of spermatozoa.

[Dual trigger with gonadotropin-releasing hormone agonist and hCG to improve oocyte maturation rate]. / Intérêt du double déclenchement par agoniste de la GnRH et hCG en cas d'antécédent d'immaturité ovocytaire en FIV/ICSI.

OBJECTIVE: This study investigates dual trigger with GnRHa and hCG as a potential treatment in patients with a history of ≥25 % immature oocytes retrieved in IVF/ICSI cycles. METHODS: This is a retrospective case-control study performed between October 2008 and December 2017. Forty-seven patients who experienced high oocyte immaturity rate (≥25 %) during their first IVF/ICSI cycle (analyzed as control group) and received a dual trigger for their subsequent cycle, were involved. During dual trigger cycles, patients received antagonist protocol and ovulation triggering using triptorelin 0.2mg and hCG. Primary endpoint was maturation rate (MR). Secondary endpoints were fertilization, D2 top quality embryo (TQE) rates, clinical pregnancy rate per fresh embryo transfer and cumulative clinical pregnancy rate per couple. RESULTS: A significant increase in MR was achieved in case of dual trigger (71.0 %) when compared to control group (47.8 %; P<0.0001). Moreover, cumulative clinical pregnancy rate yielded 46.8 % in dual trigger group, which was statistically higher than 27.6 % obtained in control group (P=0.05). However, fertilization, D2 TQE rates and clinical pregnancy rates/transfer were statistically similar when compared between the two groups. CONCLUSION: Dual trigger seems efficient for managing patients with high oocyte immaturity rate.

Medical techniques of fertility preservation in the male and female.

Therapeutic advances in many medical fields have led to the need to consider patient quality of life after curative medico-surgical treatments for malignancy. Thus, it has become a major issue for young patients to preserve the ability to become "genetic" parents, with their own gametes. While the preservation of male fertility has been an established technique for more than 30 years, it is only in the last decade that progress in cryopreservation techniques has allowed surgeons to offer successful oocyte and ovarian tissue cryobanking. However, in addition to the still experimental nature of some fertility preservation techniques, this practice also raises many ethical and moral questions.

Use of the endometriosis fertility index in daily practice: A prospective evaluation.

OBJECTIVE: To perform a prospective evaluation of postoperative fertility management using the endometriosis fertility index (EFI). STUDY: This prospective non-interventional observational study was performed from January 2013 to February 2016 in a tertiary care university hospital and an assisted reproductive technology (ART) centre. In total, 196 patients underwent laparoscopic surgery for endometriosis-related infertility. Indications for surgery included pelvic pain (dysmenorrhoea, and/or deep dyspareunia), abnormal hysterosalpingogram, and failure to conceive after three or more superovulation cycles with or without intra-uterine insemination. Multidisciplinary fertility management followed the surgical diagnosis and treatment of endometriosis. Three postoperative options were proposed to couples based on the EFI score: EFI score ≤4, ART (Option 1); EFI score 5-6, non-ART management for 4-6 months followed by ART (Option 2); or EFI score ≥7, non-ART management for 6-9 months followed by ART (Option 3). The main outcomes were non-ART pregnancy rates and cumulative pregnancy rates according to EFI score. Univariate and multivariate analyses with backward stepwise logistic regression were used to explain the occurrence of non-ART pregnancy after surgery for women with EFI scores ≥5. Adjustment was made for potential confounding variables that were significant (p<0.05) or tending towards significance (p<0.1) on univariate analysis. RESULTS: The cumulative pregnancy rate was 76%. The total number of women and pregnancy rates for Options 1, 2 and 3 were: 26 and 42.3%; 56 and 67.9%; and 114 and 87.7%, respectively. The non-ART pregnancy rates for Options 1, 2 and 3 were 0%, 30.5% and 48.2%, respectively. The ART pregnancy rates for Options 1, 2 and 3 were 50%, 60.6% and 80.3%, respectively. The mean time to conceive for non-ART pregnancies was 4.2 months. The benefit of ART was inversely correlated with the mean EFI score. On multivariate analysis, the EFI score was significantly associated with non-ART pregnancy (odds ratio 1.629, 95% confidence interval 1.235-2.150). CONCLUSION: In daily prospective practice, the EFI was useful for subsequent postoperative fertility management in infertile patients with endometriosis.

Non-ART pregnancy predictive factors in infertile patients with peritoneal superficial endometriosis.

OBJECTIVE: To study the predictive factors for non-ART pregnancy in infertile women after laparoscopic diagnosis and surgery for isolated superficial peritoneal endometriosis (SUP). STUDY DESIGN: Retrospective observational study from January-2004 to December-2015 in a tertiary care university hospital and Assisted Reproductive Technology (ART) centre. Infertile women with laparoscopic surgery for SUP (with histologic diagnosis) were included. The surgical treatment was followed by spontaneous fertility or post-operative ovarian stimulation (pOS) using superovulation (gonadotrophins)±Intra Uterine Insemination (IUI). The main outcomes were the non-ART clinical pregnancy rates and its predictive factors. RESULT(S): Over the period study, 315 women were included. Of these, 133 (42.3%) women had non-ART pregnancy. The mean time to conceive was 6 months (±6days). Univariate analysis for non-ART pregnancy after surgery showed that: (i) no difference was observed according to age, length of infertility, Body Mass Index (BMI), the rate of previous pregnancy, and the pre-operative ovarian stimulation rate; (ii) diminished ovarian reserve and previous miscarriage were higher in the non-pregnant women group (8.3 versus 19.1%, p<0.05; 3.5% versus 9%, p=0.06, respectively); (iii) the mean EFI score and pOS were higher in pregnant women (7.7 versus 7.2, p=0.02; 49.2% versus 26.7%, p<0.01); and (iv) IUI did not show any benefit for pregnancy (22% after superovulation versus 27.2% after superovulation and IUI). In the multivariate analysis, only pOS (adjusted OR 2.504, 95% CI [1.537-4.077]) and DOR (aOR 0.420, 95% CI [0.198-0.891]) remained significantly associated with the incidence of pregnancy. CONCLUSION(S): After laparoscopic surgery for peritoneal superficial endometriosis related infertility, ovarian stimulation improved pregnancy rate, while diminished ovarian reserve had a worse prognosis for pregnancy.

What threshold values of antral follicle count and serum AMH levels should be considered for oocyte cryopreservation after in vitro maturation?

STUDY QUESTION: What threshold values of ultrasonographic antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) levels should be considered for ensuring the cryopreservation of sufficient number of in vitro matured (IVM) oocytes, in cancer patients seeking fertility preservation (FP)? SUMMARY ANSWER: AFC and serum AMH values >20 follicles and 3.7 ng/ml, respectively, are required for obtaining at least 10 IVM oocytes for cryopreservation. WHAT IS KNOWN ALREADY: IVM of cumulus oocyte complexes (COCs) followed by oocyte cryopreservation has emerged recently as an option for urgent FP. Recent data have reported that, in healthy patients, 8-20 cryopreserved oocytes after ovarian stimulation would maximize the chance of obtaining a live birth. Although both AFC and AMH have been reported as predictive factors of IVM success in infertile patients with polycystic ovary syndrome (PCOS), there is a dramatic lack of data regarding the values of these parameters in oncological patients as candidates for FP. STUDY DESIGN, SIZE, DURATION: From January 2009 to April 2015, we prospectively studied 340 cancer patients, aged 18-41 years, as candidates for oocyte cryopreservation following IVM. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients had AFC and AMH measurements, 48-72 h before oocyte retrieval, regardless of the phase of the cycle. COCs were recovered under ultrasound guidance 36 h after hCG priming. Logistic regression allowed the determination of threshold values of AFC and AMH, for obtaining at least 8, 10 or 15 matures oocytes frozen after the IVM procedure. Similar analyses were performed for a final number of mature oocytes ≤2. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 340 cancer patients included, 300 were diagnosed with breast cancers, 14 had hematological malignancies and 26 underwent the procedure for others indications. Overall, the mean age of the population was 31.8 ± 4.5 years. Mean AFC and serum AMH levels were 21.7 ± 13.3 follicles and 4.4 ± 3.8 ng/ml, respectively. IVM was performed in equal proportions during the follicular or luteal phase of the cycle (49 and 51%, respectively). Statistical analysis showed that AFC and AMH values above 28 follicles and 3.9 ng/ml, 20 follicles and 3.7 ng/ml and 19 follicles and 3.5 ng/ml are required, respectively, for obtaining at least 15, 10 or 8 frozen IVM oocytes with a sensitivity ranging from 0.82 to 0.90. On the contrary, ≤2 IVM oocytes were cryopreserved when AFC and AMH were <19 follicles and 3.0 ng/ml, respectively. LIMITATIONS, REASONS FOR CAUTION: Although the potential of cryopreserved IVM oocytes from cancer patients remains unknown, data obtained from infertile PCOS women have shown a dramatically reduced competence of these oocytes when compared with that of oocytes recovered after ovarian stimulation. As a consequence, the optimal number of IVM oocytes frozen in candidates for FP is currently unpredictable. WIDER IMPLICATIONS OF THE FINDINGS: Cryopreservation of oocytes after IVM should be considered in the FP strategy when ovarian stimulation is unfeasible, in particular when markers of the follicular ovarian status are at a relatively high range. Further investigation is needed to objectively assess the real potential of these IVM oocytes after cryopreservation. Therefore, even when a good COCs yield is expected, we should systematically encourage IVM in combination with ovarian tissue cryopreservation. STUDY FUNDING/COMPETING INTERESTS: No external funding was obtained for the present study. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

[A prospective study to compare the efficiency of oocyte vitrification using closed or open devices]. / Étude prospective comparant l'efficacité de la vitrification ovocytaire en système fermé ou en système ouvert.

OBJECTIVES: Oocyte vitrification using an open device is thought to be a source of microbiological and chemical contaminations that can be avoided using a closed device. The principal purpose of this study was to compare the two vitrification protocols: closed and open system. The secondary aim was to study the effects of the storage in the vapor phase of nitrogen (VPN) on oocytes vitrified using an open system and to compare it to those of a storage in liquid nitrogen (LN). METHODS: Forty-four patients have been included in our study between November 2014 and May 2015. Two hundred and fourteen oocytes have been vitrified at germinal vesicle (GV), metaphase I (0PB) and metaphase II (1PB) stages. We vitrified 96 oocytes (59 GV/37 0PB) using a closed vitrification device and 118 oocytes (57 GV/31 0PB/30 1PB) using an open device. The vitrified oocytes were then stored either in LN or in VPN. The main outcome measures were the survival rate after warming (SR), meiosis resumption rate (MRR) and maturation rate (MR). RESULTS: The global post-thaw SR was significantly higher for oocytes vitrified using an open system (93.2%) compared to those vitrified using a closed one (64.5%; P<0.001). On the contrary, there was no significant difference in terms of global MRR and MR (82.1% vs. 87.5% and 60.7% vs. 61.2% using closed and open system respectively). The SR, MRR and the MR were not significantly different when vitrified oocytes were stored in VPN or LN (91.6, 83.8, 64.5% vs. 93.9, 89.8, 59.1% respectively). CONCLUSION: Taking into account the limits of our protocol, the open vitrification system remains the more efficient system. The use of sterile liquid nitrogen for oocyte vitrification and the subsequent storage in vapor phase of nitrogen could minimize the hypothetical risks of biological and chemical contaminations.

[Fertility preservation in women of the childbearing age: Indications and strategies]. / Préservation de la fertilité chez la femme en âge de procréer : indications et stratégies.

Advances on cryopreservation techniques now allow considering oocyte, embryo or ovarian tissue freezing for female fertility preservation. Originally developed for patients suffering from cancer, fertility preservation has rapidly invaded others medical fields, and represents now the standard of care for all young patient diagnosed with a disease that could impair fertility or having to receive possibly gonadotoxic treatment. As a result, autoimmune diseases, some genetic pathologies or iterative pelvic surgeries, at risk of premature ovarian failure, have become common indications of fertility preservation. In addition, the social egg freezing aiming at preventing the age-related fertility decline is still debated in France, although authorized in numerous countries. This review will discuss the different strategies of fertility preservation in young girls and women of reproductive age, regarding different medical or non-medical indications.

[Embryo development in two single-step media: Analysis of 2059 sibling oocytes]. / Développement embryonnaire dans 2 milieux de culture globale : étude prospective autocontrôlée sur 2059 ovocytes.

OBJECTIVE: The aim of this study was to compare embryo development cultured in two single-step media commercially available: Fert/Sage One Step® (Origio) and Continuous Single Culture® (CSC) (Irvine Scientific). METHODS: A prospective auto-controlled study of sibling oocytes from women undergoing conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) was performed in our center from February to June 2015. After fertilization, for every patient, half of oocytes were cultured in the single-step Fert/Sage One Step® (serie SAGE) and the other half in the single-step CSC®(serie CSC). Fertilization and embryo morphology rates were assessed by day 1 to day 5-6 if needed. Embryo presenting<20% of fragmentation and 4 cells at day 2, 8 cells at day 3 were qualified as "top quality". Embryo with<20% of fragmentation and 3-5 cells at day 2, 6-10 cells at day 3 were qualified as "good quality". Blastocyst B3, B4, B5 with A or B inner cell mass and A or B trophectoderm were qualified as "good quality". Transferred or frozen embryos were qualified as useful embryos. RESULTS: Sixty-two attempts of IVF and 133 of ICSI were analyzed, corresponding to 2059 inseminated or micro-injected oocytes. Fertilization rate were not different between the 2 series, respectively SAGE vs CSC (IVF: 73.4% vs 68.3% [P=0.49]; ICSI: 58.9% vs 63.8% [P=0.12]). No difference was found for embryo morphology, respectively SAGE vs CSC, at day 2 (top quality embryo at day 2 IVF: 34.4% vs 33% [P=0.98]; ICSI: 42.4% vs 44.9% [P=0.37]; and good quality embryo at day 2 IVF: 44% vs 50.2% [P=0.07]; ICSI: 64% vs 71% [P=0.35]); no difference at day 3 (top quality embryo at day 3 IVF: 19.4% vs 21.3% [P=0.61]; ICSI: 28.7% vs 27.4% [P=0.54]; and good quality embryo at day 3 IVF: 40.4% vs 50.2% [P=0.91]; ICSI: 51% vs 47.6% [P=0.47]). Blastocyst development rate were not different, respectively SAGE vs CSC (IVF: 39.9% vs 41.5% [P=0.63] with 42.9% vs 42.2% of good quality blastocyst [P=0.70]; ICSI: 41.1% vs 37.8% [P=0.18] with 32.9% vs 40.8% of good quality blastocyst [P=0.13]). No difference was found in the useful embryo rate in the 2 series SAGE vs CSC (IVF: 52.8% vs 55.2% [P=0.83]; ICSI: 62.4% vs 61.7% [P=0.70]). CONCLUSION: Embryo development and rate of useful embryos, transferred or frozen, were not different according to the embryo culture in single-step media Fert/Sage One Step® vs single-step Continuous Single Culture®.

Similar in vitro maturation rates of oocytes retrieved during the follicular or luteal phase offer flexible options for urgent fertility preservation in breast cancer patients.

STUDY QUESTION: Are in vitro maturation (IVM) rates of cumulus-oocyte complexes (COCs), retrieved from breast cancer patients seeking urgent fertility preservation (FP) before neoadjuvant chemotherapy, different between those recovered in the follicular or in the luteal phase of the cycle? SUMMARY ANSWER: The present investigation reveals no major difference in the number of COCs recovered or their IVM rates whatever the phase of the cycle at which egg retrieval is performed, suggesting that IVM is a promising tool for breast cancer patients seeking urgent oocyte cryopreservation. WHAT IS KNOWN ALREADY: FP now represents a standard of care for young cancer patients having to undergo gonadotoxic treatment. Mature oocyte cryopreservation after IVM of COCs has been proposed for urgent FP, especially in women, who have no time to undergo ovarian stimulation, or when it is contraindicated. STUDY DESIGN, SIZE, DURATION: From January 2011 to December 2014, we prospectively studied 248 breast cancer patients awaiting neoadjuvant chemotherapy, aged 18-40 years, candidates for oocyte vitrification following IVM, either at the follicular or the luteal phase of the cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum anti-Müllerian hormone and progesterone levels and antral follicle count (AFC) were measured prior to oocyte retrieval. Patients were sorted into two groups according to the phase of the cycle during which eggs were harvested (Follicular phase group, n = 127 and Luteal phase group, n = 121). Number of COCs recovered, maturation rates after 48 h of culture and total number of oocytes cryopreserved were assessed. Moreover, the oocyte retrieval rate (ORR) was calculated by the number of COCs recovered ×100/AFC. MAIN RESULTS AND THE ROLE OF CHANCE: In the Follicular and the Luteal phase groups, women were comparable in terms of age, BMI and markers of follicular ovarian status. There was no significant difference in the number of COCs recovered (mean ± SEM), 9.3 ± 0.7 versus 11.1 ± 0.8, and ORR (median (range)) 43.1 (1-100) versus 47.8 (7.7-100)%. Moreover, maturation rates after 48 h of culture (median (range)) were comparable in the follicular and luteal phase groups, 66.7 (20-100) versus 64.5 (0-100)%. Finally, the total number of oocytes cryopreserved (mean ± SEM) was similar in both groups (6.2 ± 0.4 versus 6.8 ± 0.5). LIMITATIONS, REASONS FOR CAUTION: Despite the intact meiotic competence of immature oocytes recovered during the follicular or the luteal phase, there is a dramatic lack of data regarding the outcome of IVM oocytes cryopreserved in cancer patients. WIDER IMPLICATIONS OF THE FINDINGS: IVM of oocytes may be an interesting method of FP in urgent situations. Improving the culture conditions will be needed to increase the maturation rates and the overall potential of in vitro matured oocytes. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

[Endometriosis Fertility Index, or classification of the American Society of Reproductive Medicine for postoperative endometriosis patients with infertility: Which is more relevant?]. / Endometriosis Fertility Index ou classification de l'American Society of Reproductive Medicine pour les patientes infertiles endométriosiques opérées. Lequel est le plus pertinent ?

The revised American Fertility Society classification system has been most used after surgery by all consensus on endometriosis fertility. However, it does not predict pregnancy. The EFI score has been recently developed to aim at predicting clinical pregnancy after surgery. Several study performed its external validation. It may be a useful new tool to counsel couples for personalized postoperative management.

[Laparoscopy in ART?]. / Y a-t-il une place pour la cœlioscopie dans le parcours en assistance médicale à la procréation ?

The use of laparoscopy in infertility is currently controversial. However, laparoscopic treatment of tubal and peritoneal disease, or endometriosis improves natural fecundity and ART results. The use of laparoscopy in unexplained infertility can be considered because of underestimated pelvic pathology. The result of laparoscopy may help the practitioner for choosing spontaneous pregnancy or ART postoperative management. Although there is a lack of randomized study, laparoscopy is useful for a high overall pregnancy rate (surgery and ART treatment). Rather than opposing ART and laparoscopy, the integrated approach seems better for personal management.