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.

Comparative effectiveness of gonadotropins used for ovarian stimulation during assisted reproductive technologies (ART) in France: A real-world observational study from the French nationwide claims database (SNDS).

This comparative non-interventional study using data from the French National Health Database (Système National des Données de Santé) investigated real-world (cumulative) live birth outcomes following ovarian stimulation, leading to oocyte pickup with either originator recombinant human follicle-stimulating hormone (r-hFSH) products (alfa or beta), r-hFSH alfa biosimilars, or urinaries including mainly HP-hMG (menotropins), and marginally u-hFSH-HP (urofollitropin). Using data from 245,534 stimulations (153,600 women), biosimilars resulted in a 19% lower live birth (adjusted odds ratio (OR) 0.81, 95% confidence interval (CI) 0.76-0.86) and a 14% lower cumulative live birth (adjusted hazard ratio (HR) 0.86, 95% CI 0.82-0.89); and urinaries resulted in a 7% lower live birth (adjusted OR 0.93, 95% CI 0.90-0.96) and an 11% lower cumulative live birth (adjusted HR 0.89, 95% CI 0.87-0.91) versus originator r-hFSH alfa. Results were consistent across strata (age and ART strategy), sensitivity analysis using propensity score matching, and with r-hFSH alfa and beta as the reference group.

Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: a large multicenter cohort study (14 421 frozen cycles).

STUDY QUESTION: Does the endometrial preparation protocol (artificial cycle (AC) vs natural cycle (NC) vs stimulated cycle (SC)) impact the risk of early pregnancy loss and live birth rate after frozen/thawed embryo transfer (FET)? SUMMARY ANSWER: In FET, ACs were significantly associated with a higher pregnancy loss rate and a lower live birth rate compared with SC or NC. WHAT IS KNOWN ALREADY: To date, there is no consensus on the optimal endometrial preparation in terms of outcomes. Although some studies have reported a higher pregnancy loss rate using AC compared with NC or SC, no significant difference was found concerning the pregnancy rate or live birth rate. Furthermore, no study has compared the three protocols in a large population. STUDY DESIGN SIZE DURATION: A multicenter retrospective cohort study was conducted in nine reproductive health units in France using the same software to record medical files between 1 January 2012 and 31 December 2016. FET using endometrial preparation by AC, modified NC or SC were included. The primary outcome was the pregnancy loss rate at 10 weeks of gestation. The sample size required was calculated to detect an increase of 5% in the pregnancy loss rate (21-26%), with an alpha risk of 0.5 and a power of 0.8. We calculated that 1126 pregnancies were needed in each group, i.e. 3378 in total. PARTICIPANTS/MATERIALS SETTING METHODS: Data were collected by automatic extraction using the same protocol. All consecutive autologous FET cycles were included: 14 421 cycles (AC: n = 8139; NC: n = 3126; SC: n = 3156) corresponding to 3844 pregnancies (hCG > 100 IU/l) (AC: n = 2214; NC: n = 812; SC: n = 818). Each center completed an online questionnaire describing its routine practice for FET, particularly the reason for choosing one protocol over another. MAIN RESULTS AND THE ROLE OF CHANCE: AC represented 56.5% of FET cycles. Mean age of women was 33.5 (SD ± 4.3) years. The mean number of embryos transferred was 1.5 (±0.5). Groups were comparable, except for history of ovulation disorders (P = 0.01) and prior delivery (P = 0.03), which were significantly higher with AC. Overall, the early pregnancy loss rate was 31.5% (AC: 36.5%; NC: 25.6%; SC: 23.6%). Univariable analysis showed a significant association between early pregnancy loss rate and age >38 years, history of early pregnancy loss, ovulation disorders and duration of cryopreservation >6 months. After adjustment (multivariable regression), the early pregnancy loss rate remained significantly higher in AC vs NC (odds ratio (OR) 1.63 (95% CI) [1.35-1.97]; P < 0.0001) and in AC vs SC (OR 1.87 [1.55-2.26]; P < 0.0001). The biochemical pregnancy rate (hCG > 10 and lower than 100 IU/l) was comparable between the three protocols: 10.7% per transfer. LIMITATIONS REASONS FOR CAUTION: This study is limited by its retrospective design that generates missing data. Routine practice within centers was heterogeneous. However, luteal phase support and timing of embryo transfer were similar in AC. Univariable analysis showed no difference between centers. Moreover, a large number of parameters were included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: Our study shows a significant increase in early pregnancy loss when using AC for endometrial preparation before FET. These results suggest either a larger use of NC or SC, or an improvement of AC by individualizing hormone replacement therapy for patients in order to avoid an excess of pregnancy losses. STUDY FUNDING/COMPETING INTERESTS: The authors declare no conflicts of interest in relation to this work. G.P.-B. declares consulting fees from Ferring, Gedeon-Richter, Merck KGaA, Theramex, Teva; Speaker's fees or equivalent from Merck KGaA, Ferring, Gedeon-Richter, Theramex, Teva. N.C. declares consulting fees from Ferring, Merck KGaA, Theramex, Teva; Speaker's fees or equivalent from Merck KGaA, Ferring. C.R. declares a research grant from Ferring, Gedeon-Richter; consulting fees from Gedeon-Richter, Merck KGaA; Speaker's fees or equivalent from Merck KGaA, Ferring, Gedeon-Richter; E.M.d'A. declares Speaker's fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, Theramex, Teva. I.C-D. declares Speaker's fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, IBSA. N.M. declares a research grant from Merck KGaA, MSD, IBSA; consulting fees from MSD, Ferring, Gedeon-Richter, Merck KGaA; Speaker's fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, Teva, Goodlife, General Electrics. TRIAL REGISTRATION NUMBER: N/A.

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.

IVF outcomes in patients with a history of bariatric surgery: a multicenter retrospective cohort study.

STUDY QUESTION: How does a history of dramatic weight loss linked to bariatric surgery impact IVF outcomes? SUMMARY ANSWER: Women with a history of bariatric surgery who had undergone IVF had a comparable cumulative live birth rate (CLBR) to non-operated patients of the same BMI after the first IVF cycle. WHAT IS KNOWN ALREADY: In the current context of increasing prevalence of obesity in women of reproductive age, weight loss induced by bariatric surgery has been shown to improve spontaneous fertility in obese women. However, little is known on the clinical benefit of bariatric surgery in obese infertile women undergoing IVF. STUDY DESIGN, SIZE, DURATION: This exploratory retrospective multicenter cohort study was conducted in 10 287 IVF/ICSI cycles performed between 2012 and 2016. We compared the outcome of the first IVF cycle in women with a history of bariatric surgery to two age-matched groups composed of non-operated women matched on the post-operative BMI of cases, and non-operated severely obese women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The three exposure groups of age-matched women undergoing their first IVF cycle were compared: Group 1: 83 women with a history of bariatric surgery (exposure, mean BMI 28.9 kg/m2); Group 2: 166 non-operated women (non-exposed to bariatric surgery, mean BMI = 28.8 kg/m2) with a similar BMI to Group 1 at the time of IVF treatment; and Group 3: 83 non-operated severely obese women (non-exposed to bariatric surgery, mean BMI = 37.7 kg/m2). The main outcome measure was the CLBR. Secondary outcomes were the number of mature oocytes retrieved and embryos obtained, implantation and miscarriage rates, live birth rate per transfer as well as birthweight. MAIN RESULTS AND THE ROLE OF CHANCE: No significant difference in CLBR between the operated Group 1 patients and the two non-operated Groups 2 and 3 was observed (22.9%, 25.9%, and 12.0%, in Groups 1, 2 and 3, respectively). No significant difference in average number of mature oocytes and embryos obtained was observed among the three groups. The implantation rates were not different between Groups 1 and 2 (13.8% versus 13.7%), and although lower (6.9%) in obese women of Group 3, this difference was not statistically significant. Miscarriage rates in Groups 1, 2 and 3 were 38.7%, 35.8% and 56.5%, respectively (P = 0.256). Live birth rate per transfer in obese patients was significantly lower compared to the other two groups (20%, 18%, 9.3%, respectively, in Groups 1, 2 and 3, P = 0.0167). Multivariate analysis revealed that a 1-unit lower BMI increased the chances of live birth by 9%. In operated women, a significantly smaller weight for gestational age was observed in newborns of Group 1 compared to Group 3 (P = 0.04). LIMITATIONS, REASONS FOR CAUTION: This study was conducted in France and nearly all patients were Caucasian, questioning the generalizability of the results in other countries and ethnicities. Moreover, 950 women per group would be needed to achieve a properly powered study in order to detect a significant improvement in live birth rate after bariatric surgery as compared to infertile obese women. WIDER IMPLICATIONS OF THE FINDINGS: These data fuel the debate on the importance of pluridisciplinary care of infertile obese women, and advocate for further discussion on whether bariatric surgery should be proposed in severely obese infertile women before IVF. However, in light of the present results, infertile women with a history of bariatric surgery can be reassured that surgery-induced dramatic weight loss has no significant impact on IVF prognosis. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by unrestricted grants from FINOX-Gédéon Richter and FERRING Pharmaceuticals awarded to the ART center of the Clinique Mathilde to fund the data collection and the statistical analysis. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT02884258.

[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.

[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.

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.

[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®.

[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.

Delivery rates after elective single cryopreserved embryo transfer related to embryo survival.

OBJECTIVE: The objective of this study was to assess if eSCET (elective Single Cryopreserved Embryo Transfer) outcome is related to blastomere survival rate. The final objective was to avoid multiple pregnancies and offer the best chances to women to achieve pregnancy even during their frozen-thawed embryo transfer (FET) cycles. STUDY DESIGN: Patients were included in this prospective observational study if they met the following criteria: (i) women age <37 years old; (ii) IVF of ICSI cycle rank ≤2, (iii) eSET proposed during fresh embryo transfer cycle and (iv) ≥1 good quality cryopreserved embryos available (<20% fragmentation and 4-5 blastomeres at day-2 or 7-9 blastomeres at day-3). Live birth rates (LBR) were compared into eSCET groups according to embryo survival (partially damaged or intact transferred embryo). RESULTS: We observed among selected patients, that partial loss of blastomeres (1 blastomere for day-2 embryos, 1 or 2 blastomeres for day-3 embryos) following FET cycles did not affect LBR compared with intact embryo. CONCLUSION: These results underline the relevance of eSCET as a strategy to reduce multiple pregnancies frequency without reducing LBR.

[Using an ovarian drilling by hydrolaparoscopy or recombinant follicle stimulating hormone plus metformin to treat polycystic ovary syndrome: Why a randomized controlled trial fail?]. / Drilling ovarien par fertiloscopie ou stimulation par FSH plus metformine dans le traitement du syndrome des ovaires polykystiques : pourquoi un essai thérapeutique peut être un échec.

OBJECTIVES: To evaluate pregnancy rates after randomized controlled trial (RCT) between ovarian drilling by fertiloscopy or ovarian hyperstimulation+insemination+metformine after clomifène citrate (cc) treatment fails. PATIENTS AND METHODS: Randomized controlled trial with 126 patients in each arm in 9 university centers. After 6-9 months of stimulation by cc, 2 groups were randomized: group 1, ovarian drilling with bipolar energy versus group 2: 3 months treatment by metformine followed by 3 hyperstimulation by FSH+insemination. The success rate was pregnancy rate above 12 weeks. RESULTS: RCT was stopped after the screening of 40 patients. In spite of the low number of patients, the pregnancy rate is significantly higher in medical group 8/16 versus 3/18 (p=0.04). CONCLUSION: The causes of fail of RCT were in relationship with difficulties of inclusion, with absence of final agreement by team included. Moreover, RCT between medical and surgical management is often root of difficulties for patients who decline surgical strategy. However, medical treatment appeared better than drilling in this RCT.

[Elective cryopreservation of all embryos in women at risk of ovarian hyperstimulation syndrome: prevention and efficiency]. / Cryopréservation de la cohorte embryonnaire en cas de risque d'hyperstimulation: prévention et efficacité.

OBJECTIVE: To evaluate the benefits, regarding prevention and clinical pregnancy rates, of embryos cryopreservation in patients at high risk of ovarian hyper-stimulation. PATIENTS AND METHODS: Retrospective study with 66 patients divided into two groups. Group 1 (n=24), cryopreservation of all the embryos due to high risk of OHSS. Group 2 (n=42), fresh embryo transfer despite of ovarian hyper-response (E2>4000/mL, hCG day). We performed a comparative analysis for group 1 and 2 regarding implantation, pregnancy, live birth and spontaneous abortion rates. RESULTS: No case of OHSS was observed in group 1 and 40.5 % in group 2. Fresh embryo transfer in group 2 gave the following results: 12.9 % implantation rate, 21.4 % pregnancy rate per transfer and 22.2 % spontaneous abortion. Identical implantation and pregnancy rates after frozen ET cycles were observed in both groups. Whereas live birth rates were significantly better in group 1 (15.4 % vs. 67 %, P=0.04) with a significant lower rate of spontaneous abortion (27 % vs. 11.4 %, P<0,01). DISCUSSION AND CONCLUSION: The negative impact of hyperestrogenic state seems to be limited to endometrial receptivity with no effect on oocyte or embryo quality. In situation of ovarian hyper-response, cryopreservation of all embryos with subsequent transfer of thawed embryos is an efficient strategy to avoid OHSS without decreasing pregnancy and live birth rates.

[Impact of polycystic ovary syndrome on oocyte and embryo quality]. / Influence du syndrome des ovaires polykystiques sur la qualité ovocytaire et embryonnaire.

This review analyzes the literature concerning oocyte and embryo quality, in case of in vitro fertilization (IVF) for women with polycystic ovary syndrome (PCOS). Alterations in oocyte quality, and consequently in embryo quality, may be due to endocrine and intra-ovarian paracrine changes. However, most of publications find similar biological and clinical results after IVF, with or without microinjection, for women with PCOS compared to those obtained in control populations. Subgroups of more pejorative outcome probably exist within PCOS population. Finally, obesity, which is frequent in PCOS, is clearly deleterious, and multidisciplinary care, including lifestyle modifications, is then needed.

[Nutrition and miscarriages: a literature review]. / Nutrition et fausses couches spontanées : une revue de la littérature.

Miscarriage concerns approximately 15% of pregnancies and recurrent fetal loss (RFL) constitute a particular situation concerning approximately 1% of women. The etiologic inquiry is often disappointing. Nutritional factors represent a promising aspect, insufficiently investigated even if numerous studies underline their impact on fertility, gametogenesis, embryonic development and pregnancies outcome. Obesity is considered as an independent risk factor for miscarriage, involved in oocyte and embryo quality, but also in endometrial receptivity. The male part involved in miscarriage was for a long time underestimated, neglecting the role of sperm in embryo development. If conventional sperm analysis remains essential, new investigations have to be considered such as sperm DNA or oxidant stress evaluation. It is particularly important to take into account nutritional factors as favoring miscarriage because they represent a flexible factor on which intervention is possible to improve pregnancy outcome, with toxics eviction and recommendations for diversified and well-balanced food. At last, effects of nutritional complements for miscarriage prevention remain controversial.

[Outcome of embryo vitrification compared to slow freezing process at early cleavage stages. Report of the first French birth]. / Issue de la vitrification des embryons précoces versus congélation lente. Rapport de la première naissance française.

OBJECTIVES: Since the end of 2010, France by "l'Agence de Biomédecine" has validated the embryo vitrification procedure as an improvement of the slow freezing method. We presented here data concerning biological and clinical outcomes from a prospective observational study where early cleavage stage good quality embryos were vitrified and warmed. We compared these results to those of a retrospective series where embryos were thawed after a slow freezing procedure (SF). We report also the first French live birth following embryo vitrification. PATIENTS AND METHODS: In all, 58 cycles of frozen-thawed embryo transfers (FET) following vitrification were prospectively included and compared with 189 FET from SF method. Primary end points were the (i) survival rate (SR) (% of embryos with ≥50% post-thaw intact blastomeres), (ii) intact survival rate (ISR) (% of embryos with 100% post-thaw intact blastomeres) and (iii) survival blastomeres index (SBI) (% of post thaw intact blastomeres per survival embryo). Secondary end point was the clinical pregnancy rate (CPR) defined as the presence of an intra-uterine gestational sac with positive foetal heart beat. We report here the first French live birth following embryo vitrification. RESULTS: In all, 87 and 412 embryos have been thawed following vitrification and SF, respectively. We observed a highly significant increase of SR, ISR et SBI respectively when thawing concerned vitrified embryos rather than those from SF method (98.3±13.1% vs. 77.3±32.0%, P<10(-4); 88.2±28.3% vs. 47.7±41.4%, P<10(-4); 97.7±6.1% vs. 87.3±14.4%, P<10(-4)). Furthermore, CPR were of 32.7% (19/58) and of 18.5% (35/189) following FET performed after vitrification or SF and thawing (P=0.03), respectively. The live birth of two healthy girls occurred following a caesarean section after 38 weeks of amenorrhea the 8th of August 2011. DISCUSSION AND CONCLUSION: We experienced in our study that the post-thaw survival of vitrified embryos was significantly better than those of embryos resulting from SF. Then, a better CPR per thawed embryo cycle was observed following vitrification.

[Fertility after endometrial osseous metaplasia elective hysteroscopic resection]. / Fertilité après résection élective hystéroscopique de lésions de métaplasie ostéoïde de l'endomètre.

OBJECTIVES: The endometrial osseous metaplasia is a rare disease which is characterized by the presence of osseous tissue in endometrium. It is often diagnosed in women with secondary infertility. The main objective of this work is to evaluate fertility after elective resection of osteoid metaplasia endometrial lesions by operative hysteroscopy in infertile women. PATIENTS AND METHOD: Retrospective and descriptive series of 7 cases observed in the Woman and Child department, CHU Jean-Verdier. The 7 women were in reproductive age, of African origin, with secondary infertility after abortions concerning 6 out of the 7 patients. RESULTS: In all cases, endovaginal pelvic ultrasound has raised endometrial calcification, and diagnostic hysteroscopy highlighted endometrial osteoid metaplasia. The operative hysteroscopic procedure consisted of elective diathermic resection to handle endometrial insertion of bone chips. A second diagnostic hysteroscopy was systematically done. It showed no recurrence. Six of the 7 patients began pregnancy, 3 spontaneously and 3 after IVF/ICSI in the first year following the hysteroscopic treatment. The evolution of pregnancies has been marked by 2 normal deliveries, 1 spontaneous miscarriage and then an ectopic pregnancy in one patient, 1 growth retardation intrauterine requiring caesarean at 38 SA, 1 HELLP syndrome in a twin pregnancy requiring ceasarean at 27 SA followed normal labor at term and 1 pregnancy lost sight. DISCUSSION AND CONCLUSION: Hysteroscopic elective resection seems to be the treatment of choice with a good prognosis on subsequent fertility.