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Objective: To describe the use, efficacy and safety profile of follitropin delta in women undergoing IVF/ICSI in routine clinical practice after one treatment cycle., Study Design: This was a French multicenter, prospective, observational study conducted in 14 fertility centers between June 2020 and June 2021. During this period, 248 women undergoing IVF or ICSI were treated with follitropin delta for the first time. Women were followed up to 10-11 weeks after the first fresh or frozen embryo transfer. The main outcomes were use of dosing algorithm, follitropin delta dosing patterns, ovarian response, pregnancy, and adverse drug reactions in routine clinical practice., Results: The analyzable population consisted of 223 patients with mean ± SD age of 33.0 ± 4.4 years, body weight of 65.7 ± 11.8 kg, and the median (IQR) AMH level was 2.6 (1.5-4.0) ng/mL. For 193 patients (86.5 %) it was the first IVF/ICSI cycle and for 30 (13.5 %) the second. The algorithm was used for the calculation of the starting dose for 88.3 % of the patients. The mean daily starting dose of follitropin delta was 11.4 ± 4.1mcg for the whole analyzable population and 14.4 ± 5.2 mcg for the sub-group of 26 patients dosed without the algorithm. The mean duration of stimulation with follitropin delta was 10.8 ± 5.2 days. The mean total dose of follitropin delta administered was 122.2 ± 80.0 mcg. An antagonist protocol was used in 90.3 % of patients. The mean ± SD number of oocytes retrieved among patients that started stimulation was 11.3 ± 6.8 and 46.1 % of patients achieved the targeted response of the algorithm of 8-14 oocytes retrieved. A fresh transfer was performed for 77.6 % of patients; the mean ± SD number of embryos transferred was 1.3 ± 0.5. The implantation rate was 36.0 %. Per started cycle, clinical pregnancy was reported in 35.0 % of the patients and ongoing pregnancy in 29.6 %. In total, 5 patients (2.2 %) reported an event of OHSS., Conclusion: Clinical results as collected in routine clinical practice are promising, showing a favorable effectiveness-safety profile of follitropin delta for a very varied patient population (including anovulatory PCOS, very poor responders, or non-IVF naïve patients). These real-world data complement results from clinical trials and provide useful information for usual clinical practice within a heterogeneous population group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Study Question: Can the Poor Responder Outcome Prediction (PROsPeR) score identify live birth outcomes in subpopulations of patients with poor ovarian response (POR) defined according to the ESHRE Bologna criteria (female age, anti-Müllerian hormone (AMH), number of oocytes retrieved during the previous cycle (PNO) after treatment with originator recombinant human follitropin alfa?, Summary Answer: The PROsPeR score discriminated the probability of live birth in patients with POR using observational data with fair discrimination (AUC ≅ 70%) and calibration, and the AUC losing less than 5% precision compared with a model developed using the observational data., What Is Known Already: Although scoring systems for the likelihood of live birth after ART have been developed, their accuracy may be insufficient, as they have generally been developed in the general population with infertility and were not validated for patients with POR. The PROsPeR score was developed using data from the follitropin alfa (GONAL-f; Merck KGaA, Darmstadt, Germany) arm of the Efficacy and Safety of Pergoveris in Assisted Reproductive Technology (ESPART) randomized controlled trial (RCT) and classifies women with POR as mild, moderate or severe, based upon three variables: female age, serum AMH level and number of oocytes retrieved during the previous cycle (PNO)., Study Design, Size, Duration: The external validation of the PROsPeR score was completed using data derived from eight different centres in France. In addition, the follitropin alfa data from the ESPART RCT, originally used to develop the PROsPeR score, were used as reference cohort. The external validation of the PROsPeR score l was assessed using AUC. A predetermined non-inferiority limit of 0.10 compared with a reference sample and calibration (Hosmer-Lemeshow test) were the two conditions required for evaluation., Participants/materials, Setting, Methods: The observational cohort included data from 8085 ART treatment cycles performed with follitropin alfa in patients with POR defined according to the ESHRE Bologna criteria (17.6% of the initial data set). The ESPART cohort included 477 ART treatment cycles with ovarian stimulation performed with follitropin alfa in patients with POR., Main Results and the Role of Chance: The external validation of the PROsPeR score to identify subpopulations of women with POR with different live birth outcomes was shown in the observational cohort (AUC = 0.688; 95% CI: 0.662, 0.714) compared with the ESPART cohort (AUC = 0.695; 95% CI: 0.623, 0.767). The AUC difference was -0.0074 (95% CI: -0.083, 0.0689). This provided evidence, with 97.5% one-sided confidence, that there was a maximum estimated loss of 8.4% in discrimination between the observational cohort and the ESPART cohort, which was below the predetermined margin of 10%. The Hosmer-Lemeshow test did not reject the calibration when comparing observed and predicted data (Hosmer-Lemeshow test = 1.266688; P = 0.260)., Limitations, Reasons for Caution: The study was based on secondary use of data that had not been collected specifically for the analysis reported here and the number of characteristics used to classify women with POR was limited to the available data. The data were from a limited number of ART centres in a single country, which may present a bias risk; however, baseline patient data were similar to other POR studies., Wider Implications of the Findings: This evaluation of the PROsPeR score using observational data supports the notion that the likelihood of live birth may be calculated with reasonable precision using three readily available pieces of data (female age, serum AMH and PNO). The PROsPeR score has potential to be used to discriminate expected probability of live birth according to the degree of POR (mild, moderate, severe) after treatment with follitropin alfa, enabling comparison of performance at one centre over time and the comparison between centres., Study Funding/competing Interest(s): This analysis was funded by Merck KGaA, Darmstadt, Germany. P.L. received grants from Merck KGaA, outside of the submitted work. N.M. reports grants, personal fees and non-financial support from Merck KGaA outside the submitted work. T.D.H. is Vice President and Head of Global Medical Affairs Fertility, Research and Development at Merck KGaA, Darmstadt, Germany. P.A. has received personal fees from Merck KGaA, Darmstadt, Germany, outside the submitted work. C.R. has received grants and personal fees from Gedeon Richter and Merck Serono S.A.S., France, an affiliate of Merck KGaA, Darmstadt, Germany, outside the submitted work. P.S. reports congress support from Merck Serono S.A.S., France (an affiliate of Merck KGaA, Darmstadt, Germany), Gedeon Richter, TEVA and MDS outside the submitted work. C.A., J.P., G.P. and R.W. declare no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To compare follicular flushing with a double-lumen needle with direct aspiration on the number of oocytes collected in a poor responder population in IVF., Study Design: We conducted a randomized controlled prospective single-center study between March 2011 and June 2016 at the ART center in the Medico-Surgical and Obstetric Center in Schiltigheim, France. Patients undergoing IVF who had ≤ 4 follicles ≥ 14 mm on the day of HCG administration were recruited and then randomized to one of two groups : simple aspiration group (= NO FLUSH) with a single-lumen 17-gauge needle or follicular flushing group (= FLUSH) which underwent oocyte puncture with aspiration and follicular flushing with a double-lumen 17-gauge needle. The primary end-point was the number of oocytes collected. Secondary assessment criteria were the fertilization rate, the number of transferable embryos, the number of clinical pregnancies and their outcome., Results: 252 patients were included: 127 in the Flush group and 125 in the No flush The number of oocytes retrieved per patient was significantly lower in the FLUSH group: 2.41 than in the NO FLUSH group: 3.42 (p < 0.001). The number of transferable embryos, fertilization rate (68.8 % in the FLUSH group versus 75 % p = 0.682), or pregnancy rate weren't different but (15 versus 13). However the number of failed punctures was significantly higher in the FLUSH group (11 % versus 3.2 % p = 0.016) and the duration of oocyte retrieval was significantly longer in the FLUSH group where the median time was 10 min whereas it was only 7 min in the NO FLUSH group, p < 0.001 CONCLUSION: Follicular flushing in poor responders is not beneficial and could be detrimental with an increasing procedure time and less oocytes retrieved., Competing Interests: Declaration of Competing Interest The authors state that they have no conflicts of interest in relation to this study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Research Question: What is the real-world effectiveness of Fertistartkit® in women undergoing assisted reproductive technology (ART)?, Design: Retrospective cohort study including anonymized data of women undergoing ovarian stimulation for ART with Fertistartkit between April 2016 and November 2017 and follow-up of clinical outcomes up to February 2018. Data were collected from the electronic patient databases of 12 French ART centres. The main outcome was number of oocytes retrieved. All data were categorized according to female age (<25, 25-29, 30-34, 35-37, 38-39 and >39 years)., Results: A total of 1006 cycles from 914 women treated with Fertistartkit were included. At the time of first ovarian stimulation in the study, women were 34.9 ± 5.0 years old, with a median body mass index of 22.7 kg/m². Couples had been infertile for more than 4 years, with all patterns of causes of infertility. Ovarian stimulation was started with a median dose of 300 IU (interquartile range [IQR]: 150-300 IU) of Fertistartkit for 10 days (IQR: 9-11 days), so a median total dose of 2700 IU (IQR: 1800-3300 IU). The mean number of oocytes retrieved per cycle was 9.5 ± 6.8, and the mean number of mature oocytes per cycle was 7.4 ± 5.5. The obtained ongoing pregnancy per started cycle was 26.0% (95% confidence interval [CI]: 24.1-27.9) and the obtained ongoing pregnancy per puncture was 27.0% (95% CI: 25.0-29.0)., Conclusions: This is the first cohort to describe Fertistartkit treatment management in real-life conditions. The real-world data show that Fertistartkit is an effective option for ovarian stimulation., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine whether there is a difference between the known gestational age in pregnancies conceived after IVF and the estimated gestational age based on the crown-rump length (CRL) measurement during the first trimester., Design: We retrospectively (between 2007 and 2012) studied a cohort of 6,739 patients who underwent ultrasonography between 11 and 13+6 weeks of amenorrhea., Setting: Hospital., Patient(s): Group A consisted of 6,621 patients with regular menses whose term was calculated based on the date of their last menstrual period (LMP). Group B consisted of 529 patients whose pregnancies had been achieved by IVF and in whom term was calculated based on the date of fresh or frozen ET., Intervention(s): None., Main Outcome Measure(s): The gestational age difference was obtained by comparing the age obtained by measuring the CRL (Robinson's curve) with the gestational age calculated in accordance with LMP in group A or with ET day in group B., Result(s): The gestational age difference was significantly more in group B (2.3 days vs. 0.84 days in group A). We found a significant difference regarding biochemical markers for trisomy 21 to the detriment of group B with a significantly reduced pregnancy-associated protein P-A multiple of median (0.78 vs. 0.92)., Conclusion(s): There appears to be a small difference in CRL development between spontaneous pregnancies and pregnancies conceived by assisted reproductive technology (ART). Specific ultrasonographic curves for pregnancies conceived by ART would be more relevant and precise. The underlying pathophysiological mechanisms are not very clear and offer possibilities for future research., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficiency of our treatment of vaginal infection for couples included in an IVF program., Patients and Methods: Microbiologic screening of vaginal flora and semen has been performed one month prior to in vitro fertilization for 951 couples in 2000. Antibiotic treatment was prescribed in case of positive culture., Results: Positive microbial growths were observed from endocervical and vaginal cultures in 218 women (22.9%). The clinical pregnancy rate was 30.29% in the group of patients without growth and 30.27% in the group with positive microbial growth. The implantation rate was significantly diminished in case of bacterial growth: 14.6 compared to 19.3% (P <0.02) for sterile endocervical culture. Five main bacterial species were found at the cervical level: Candida albicans (69 cases), Ureaplasma urealyticum (49 cases), Gardnerella vaginalis (43 cases), Streptococcus B or D (24 cases) and Escherichia coli (22 cases). Positive cultures from both vagina and semen were observed for 77 couples whose clinical pregnancy rate was 19.5 vs 36.2% in case of vaginal infection alone (P <0.01) with a spontaneous miscarriage rate of 46.7 compared to 17.6% (P <0.01)., Discussion and Conclusion: Endocervical microorganisms, even treated with adapted antibiotics, may affect embryonic implantation. Positive culture from both female and male partner may enhance this negative effect. In this case, the best strategy would be to cancel the IVF treatment.

Objective: The transfer of a single embryo would avoid obstetrical and neonatal complications due to multiple pregnancies. We studied the clinical value of both uterine and embryological parameters to define precise conditions allowing a single embryo transfer without decreasing pregnancy rates., Patients and Methods: Endometrial parameters expressed by a uterine score together with biological criteria of 131 in vitro fertilization or intracytoplasmic sperm injection attempts were retrospectively analysed., Results: Two hundred and sixty-two day-3 embryos were replaced through 131 transfers. Fifty-seven pregnancies were induced and 16 twins were obtained. The clinical pregnancy rate was 35.9% and the embryonic implantation rate 24.0%. After the transfer of two embryos, successful implantation was determined by the occurrence of top-quality embryos and simultaneously by a receptive endometrium. The uterine pulsatility index was significantly decreased for twin compared to singleton pregnancies., Discussion and Conclusion: This study confirms that a uterine score constitutes a powerful tool for evaluating the uterine receptivity. This parameter has to be taken into account as well as the embryonic quality, in order to optimise the success rate. Young patients with at least two top-quality embryos available, a high uterine score and a low pulsatility index, have a high risk of multiple births and are suitable for a single-embryo transfer.

Objective: To determine the homocysteine evolution during ovarian stimulation in IVF or ICSI protocols and in, a second time, to evaluate the role of hyperhomocysteine as thrombotic risk factor for the treated patients., Material and Methods: Plasma homocysteine was determined three times for each of 31 women included in an IVF/ICSI program. Dosages were realised before stimulation, after gonadotrophin-releasing hormone agonist treatment (GnRH) and on the day of hCG injection. Vitamin B12 and folates were determined before stimulation. In case of hyperhomocysteinemia, a research of APCR (Activated Protein C Resistance) was realised., Results: Five hyperhomocysteinemia cases were discovered (16.12% of studied population). APCR was found in a patient with hyperhomocysteinemia (14 mumol/L, before stimulation). Molecular biology has confirmed an heterozygous mutation of factor V Leiden. During the ovarian stimulation the evolution of homocysteine was independent of the 17 beta oestradiol evolution., Conclusion: The prevalence of hyperhomocysteinemia was not significative according to the limited size of the studied population. The increase of oestradiol during induction protocols is unrelated to the homocysteine level. This work must be continued with largest population to have better knowledge of the prevalence of hyperhomocysteinemia among women included in ovarian stimulation protocols.

One of the main problems concerning IVF units is the need to decrease the occurrence of multiple pregnancies in their practice without affecting the overall success rate. Different embryological parameters concerning every step of the early embryo development are known to have some predictive value for implantation potential. In this prospective study, a pronuclear scoring system was used to classify zygotes into six patterns from 0 to 5. Cleaved, day 3 embryos developed from pattern 0 zygotes, which was described as the normal pattern, were transferred when available. For each zygote pattern, the subsequent embryological development was analysed. Pattern 0 zygotes led to significantly more 'good quality' embryos with higher implantation potential than embryos developing from the other zygote patterns (P < 0.01). Embryo transfers including at least one pattern 0 resulted in significantly more pregnancies than transfers without any pattern 0 zygotes (39.3 versus 19.7%, P < 0. 01). No relationship between clinical parameters (age of female partner, infertility cause) and zygote pattern distribution was demonstrated.

The aim of the study was to assess the psychological repercussions of IVF + ICSI on the male partner of infertile couples and on the couples and on the couple itself. The preliminary work has been done on the 23 couples in the waiting list of an ICSI cycle in A. Beclere hospital in Clamart. All couples respond to the same questionnaire. The two members of the couples were present in a semi-structured interview by 2 clinical psychologists. This ICSI scheme requires a complete change about the biological paternity. For infertile men, getting embryos work as a real reparation of their wounded ego, and the guilt goes from the man to the women when embryos are obtained. This study shows that infertile couples involved in IVF + ICSI have not the same concerns that doctors. Genetic abnormality transmission is not mentioned. On the opposite the male patients are strongly concerned by obtention of embryos which restore their fertility power. At this stage, female patients have to prove by carry out a pregnancy that they are as "good" as their partner.

The infertility in women with an abnormal uterus seems a subject of controversy. The prognosis of in vitro fertilization among these patients with such an anomaly is even less founded. The results of in vitro fertilization have been only studied with few patients and recently. Through the literature, we will focus step by step, on the impact of uterine anomalies on natural reproduction, then the impact of metroplasty on natural reproduction, the role of anomalies on the endometrium quality and lastly, the results of Assisted Rerpoductive Techniques with women with such an anomaly. It seems that the main risk is obstetric complications such as spontaneous abortion or premature delivery, not implantation failure. However, when infertility exists, surgical treatment tends to improve the pregnancy rate for some. [Copyright &y& Elsevier]