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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.)

Research Question: Is luteal phase stimulation capable of improving fertility preservation?, Materials and Methods: We performed a retrospective cohort study of consecutive ovarian stimulations, during July 2012 and September 2018 at Strasbourg University Teaching Hospital in France. Enrollment criteria were patients aged below 40 who had been referred to our center following a diagnosis of cancer or requiring gonadotoxic treatment. All patients enrolled had regular menstrual cycles and normal ovulation. Non-enrollment criteria were an expected low ovarian response (defined by an anti-Müllerian hormone (AMH) level <0.75μg/L and/or an antral follicle count inferior (AFC) inferior than 5), polycystic ovarian syndrome, amenorrhea, prior history of infertility or gonadotoxic treatment. The primary endpoint is the number of mature oocytes (metaphase II) obtained. Secondary outcomes were oocyte yields obtained, stimulation duration, initial gonadotropin dose and total gonadotropin dose., Results: A total of 100 patients were included: 20 in luteal phase and 80 in follicular phase. A larger number of mature oocytes was obtained in luteal phase versus follicular phase (13.1+/8.0 versus 9.2+/-5.8 with p=0.01). A greater amount of total (mature and immature) oocytes was obtained in luteal phase versus follicular phase with a significant difference (16.8+/-9.3 versus 11.8+/-7.3 with p=0.01). No difference was found for the initial and total doses of gonadotropin., Conclusions: Luteal phase stimulation has the advantage of a better flexibility with positives results as to the number of oocytes obtained in fertility preservation., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: The objective of this study was to assess the impact on the clinical pregnancy rate of luteal phase progesterone treatment in patients being prepared for natural cycle frozen embryo transfer (FET) with induced ovulation., Material and Methods: This retrospective cohort study collect all the FET protocols over a 6-month period at Strasbourg University Hospital fertility unit between December 2016 and May 2017. In total 293 consecutive patients with regular menstrual cycles were prepared for natural cycle FET during this period. All patients had an embryo cryopreservation secondary to in vitro fertilisation (IVF) or by intracytoplasmic sperm injection (ICSI). There were 2 protocols during this period and patients either received or did not received progesterone. Ovulation was routinely triggered in all patients by injection of choriogonadotrophin alfa. Patients in the treated group received vaginal natural micronized progesterone treatment of 400mg daily, starting on the day of ovulation. The principal assessment criterion was the occurrence of pregnancy., Results: In total, 231 patients were analysed: 108 in the group not receiving progesterone and 123 in the group receiving progesterone. Patient characteristics were comparable between groups. A higher clinical pregnancy rate (39% vs. 24.1%, p=0.02; 95CI [1.10; 3.74]) was recorded in the treated group., Conclusions: Our results suggest that luteal phase support with vaginal progesterone statistically increases the clinical pregnancy rate following hCG-triggered natural cycle FET and that it should be used more widely., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

A recent adverse effect of a paracervical block (cardiac arrest) occurred during an oocyte retrieval (OR), forcing us to reconsider our pain management during OR. Since then, we decided to use intravaginal lidocaine gel as analgesia during OR., Objectives: To evaluate the pain during OR after intravaginal lidocaine gel analgesia and to evaluate the motivations of women choosing this technique., Methods: A monocentric observational study was performed on 200 patients. Pain was measured using a numeric pain scale during and after oocyte retrieval. The tolerance of the procedure was evaluated through a patient questionnaire., Results: Median maximal pain was 5±2.3 (0-10) per-retrieval and 3±2.2 (0-10) post-retrieval. The procedure was considered bearable by 85.5% of the patients and 81.5% of them would choose this method in case of new oocyte retrieval. No adverse effect occurred during the study., Conclusion: The use of intravaginal lidocaine gel seems an acceptable analgesia alternative during oocyte retrieval., (Copyright © 2016 Elsevier Masson SAS. 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.)

Fragile X syndrome (FraX) is caused by the expansion of an unstable CGG repeat located in the Fragile X mental retardation 1 gene (FMR1) gene. Preimplantation genetic diagnosis (PGD) can be proposed to couples at risk of transmitting the disease, that is, when the female carries a premutation or a full mutation. We describe two new single-cell, single-round multiplex PCR for indirect and direct diagnosis of FraX on biopsied embryos. These tests include five unpublished, highly heterozygous simple sequence repeats, and the co-amplification of non-expanded CGG repeats for the direct test. Heterozygosity of the new markers ranged from 69 to 81%. The mean rate of non-informative marker included in the tests was low (26% and 23% for the new indirect and direct tests, respectively). This strategy allows offering a PGD for FraX to 96% of couples requesting it in our centre. A conclusive genotype was obtained in all cells with a rate of cells presenting an allele dropout ranging from 17% for the indirect test to 26% for the direct test. The new indirect test was applied for eight PGD cycles: 32 embryos were analysed, 9 were transferred and 3 healthy babies were born. By multiplexing these highly informative markers, robustness of the diagnosis is improved and the loss of potentially healthy embryos (because they are non-diagnosed or misdiagnosed) is limited. This may increase the chances of success of couples requesting a PGD for FraX, in particular, when premature ovarian insufficiency in premutated women leads to a reduced number of embryos available for analysis.

Objectives: Recurrent miscarriages are a current consultation pattern. Etiologic evaluation is classically proposed and preventive therapy should be discussed. We wanted to study our University Hospital pregnancies outcomes, following 3 repetitive early miscarriages, and how those patients are managed., Materials and Methods: A 10-years retrospective study has been performed in our center, with 296 patients found having a three-repetitive miscarriage experience. Information about diagnostic evaluation following miscarriages, preventive therapy initiation, and next pregnancy outcome has been provided., Results: Around 62.5% of the patients experienced a life-birth. When investigations were done (n=148), a 64.9% part of the patients had abnormal results. Life-birth rate was more important when there were normal karyotypes or no thrombophilia found (respectively p equal 0.30 and 0.45). We noticed a better prognostic in the group of patients with normal investigations results who had a preventive therapy (n=20, 85% of life-birth, P=0.19)., Conclusion: When done, investigations for recurrent miscarriages, allow the finding of an abnormality in two thirds of cases. Wonderingly, outcomes are very encouraging since that almost two thirds of the patients experienced life-birth. Investigations indications, results interpretations, and consecutive therapy should be well thought but preventive therapy seems to be efficient in the normal results patient group., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objective: The aim of this study was to present the situation of embryo donation in France and around the world, to expound the difficulties of its practice and the results obtained in our centre 3 years after the introduction of this procedure., Patients and Methods: Embryo donation in France is controlled by implemented decrees published between 1999 and 2004. The couples, who have stored frozen embryos since at least two years, were contacted for a pluridisciplinary medical consultation. The indication of embryo donation was evaluated for the recipients through a pluridisciplinary approach., Results: Among the interviewed couples, 16.7% have chosen embryo donation but only half of them have completed the procedure (6% of the couples with frozen embryos). The main indications for embryo donation were a double sterility, unexplained genetic disease, ART failures (poor fertilization or bad embryo quality) and oocyte donation when the delay was too long for the couples. The pregnancy rate was 28.6% after the 21 first embryo transfers., Discussion and Conclusion: The results of embryo donation confirm the international experience both considering the poor number of donated embryos, medical indications and results. Embryo donation has its place among ART techniques, but one should not ignore the general debate on ethical questions raised by this procedure.

Standard monitoring of controlled ovarian hyperstimulation (COH) includes hormone assays (estradiol, LH, progesterone) and regular pelvic ultrasound examination. We report a randomized study on an attempt to simplify monitoring of COH. Ultrasound monitoring of the cycle alone did not affect pregnancy rates and did not increase the risks of OHSS. These results encourage the future simplification of stimulation protocols.

The aim of metroplasties is to restore a normal uterine anatomy to improve obstetrical outcomes in some uterine malformations. The hysteroscopic septoplasty cures the septate uterus. It is an effective procedure in the case of recurrent abortion losses. It probably improves the rate of live birth in women without obstetrical antecedent. For some authors, it could be considered at the time of the diagnosis, because of the simplicity of the gesture and the low complication rate. The enlarging hysteroscopic metroplasty has certainly a positive impact on the obstetrical outcome in patients presenting a uterine hypotrophy or dysmorphy, in particular in women exposed in utero to DES. However, the proofs are poor to propose this procedure as first-line treatment, apart from specific cases such as old null gravid patient or before inclusion in an Assisted Reproductive Techniques (ART) program.

There is no simple answer to the problem of fertility after one ectopic pregnancy. Results reported in the literature have been satisfactory with rate of subsequent pregnancy about 60% and the risk of new ectopic pregnancy (EP) around 28%. We have deliberately excluded studies before 1990 except when the methodology was particularly good or the treatment particularly interesting. Strict and exhaustive criteria were lacking in most of these studies due to widely varying aims, the prospective or retrospective nature of the data, the number of patients included, and varying therapeutic decision-making schemes. Many patients were lost to and no mention is given concerning the proportion of patients who desired a subsequent pregnancy. Infertility factors were not considered in most cases. We were looking for fertility results according to treatment used. Among the 50 studies we retained, pregnancy rates after ectopic pregnancy were satisfactory whatever treatment was used, with laparoscopy being the gold standard. Medical treatment was at least as effective as surgical treatment. Associated infertility factors appeared to be the most important for fertility outcome. It is unfortunate that so few study have analyzed outcome in these patients without considering risks factors of EP, infertility factors and the proportion of women who attempted to conceive again.

We have developed a new allele-specific amplification method for the preimplantation genetic diagnosis (PGD) of spinal muscular atrophy (SMA; Werdnig-Hoffmann disease) from a single cell. This method is based on the detection of the deletion of exon 7 of the telomeric copy of the survival motor neurone (SMN(t)) gene. An oligonucleotide was designed to be specific to the SMN(t) nucleotidic sequence with exonic mismatch G (for SMN(t))-->A (for SMN(c)) at its 3' end. This test produces reliable PCR products in 95% of single lymphoblasts (85/88) tested as well as in 16/16 blastomeres from normal controls. Specificity analysis showed that we were able to detect homozygous deletion of the SMN(t) gene in 99% of single lymphoblasts (103/104) from a SMA patient. No contamination was detected in 68 blanks tested. Multiple cell and DNA dilution analysis revealed that the test is accurate and specific up to 100 pg DNA and should thus also be suitable for PGD at the blastocyst stage. This rapid procedure requires a single round of fluorescent PCR and no restriction digestion, while previously described single cell methods include nested PCR followed by restriction enzyme digestion. Two PGD cycles for SMA using this procedure were performed in our centre.

After treatment for neoplasia, a young patient can nowadays hope to be pregnant. The aim of this paper is to establish a review of the literature about cryopreservation of oocytes and ovarian tissue, and in vitro maturation of oocytes. These studies also concern patients for which ovarian stimulation is difficult, such as PCOS. These techniques could also facilitate the creation of an oocyte bank as the one already existing for sperm. So far the main studies published, in spite of very timid first results, allow us to look to a great future for cryopreservation and in vitro maturation of oocytes.

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.