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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., Competing Interests: Declaration of competing interest MG has received fees from Merck Healthcare KGaA, Darmstadt, Germany, as a medical expert for this study, and lecture fees from Merck KGaA, Darmstadt, Germany, MSD, Ferring, IBSA, Gedeon Richter, Theramex, General Electric, Novartis, Besins Healthcare. I-CD has received fees from Merck Healthcare KGaA, Darmstadt, Germany, as a medical expert for this study, and lecture fees from Merck KGaA, Darmstadt, Germany, MSD, Ferring, IBSA, Gedeon Richter, and Theramex. FR and EH are employees of HEVA, Lyon, France. LL, FP, SP, and CC-B are employees of Merck Santé, Lyon, France, an affiliate of Merck KGaA, Darmstadt, Germany. PV, JES, and TDH are employees of Merck Healthcare KGaA, Darmstadt Germany. CH is an employee of Merck KGaA, Darmstadt Germany. MB has received fees from Merck Healthcare KGaA, Darmstadt, Germany, as a medical expert for this study, and lecture fees from Merck KGaA, Darmstadt, Germany., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Economic evaluations of the value-for-money of Medically Assisted Reproduction (MAR) interventions are increasingly important due to growing pressure on healthcare budgets. Although such evaluations are commonplace in the published literature, the number/methodological complexity of different evaluations available, and the challenges specific to MAR interventions, can complicate the interpretation of such analyses for fertility treatments. This article aims to serve as an educational resource and provide context on the design/interpretation of economic analyses for MAR interventions. Several areas are relevant for first-line providers and decision makers: scope of analysis, comparator used, perspective/time horizon considered, outcomes used to measure success, and how results from cost-effectiveness studies can be summarised and used in clinical practice. We aim to help clinicians better understand the strengths/weaknesses of economic analyses, to enable the best use of the evidence in practice, so resources available for MAR interventions can provide maximum value to patients and society., Competing Interests: Declaration of competing interest The authors in this manuscript were qualified according to ICMJE criteria and has received no fees for their authorship. ML and TDH are employees of Merck Healthcare KGaA, Darmstadt, Germany. Outside of the submitted manuscript, MPC has received honoraria for a lecture from Merck KGaA, Darmstadt, Germany; AR has received, individually or as part of his institution, grants, honoraria or consultation fees from Merck Healthcare, Darmstadt, Germany, Ferring and MSD. The remaining authors report no disclosures., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The aim is to report the first live-birth following ICSI using spermatozoa previously vitrified in a Stripper Tip., Principal Results: A 34-year-old cryptozoospermic man was enrolled in a sperm vitrification program. After failure of conventional freezing technique, spermatozoa were vitrified using two carriers: a commercially-available, Cell Sleeper, and a "home-made" one, Stripper Tip. This man and his 30-year-old wife underwent an ICSI attempt using vitrified-warmed spermatozoa from these devices. All frozen-warmed spermatozoa were quickly recovered. Among the oocytes retrieved, six were injected with sperm from the Cell Sleeper, and seven with sperm from the Stripper tip, leading to 4 embryos in each case. Two embryos, arising from sperm frozen in the Stripper tip, were transferred, resulting in a healthy live-birth., Conclusions: This is the first successful delivery following the use of spermatozoa frozen in an original device, the Stripper Tip, giving a promising prospect for managing severe male infertilities., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Clinical outcomes of 291 day-5 blastocyst transfers carried out between January 2012 and March 2016 were retrospectively compared according to their quality at day 2 and 3. Inclusion criteria were female age younger than 37 years; first or second IVF and intracytoplasmic sperm injection cycle; quality of the transferred blastocyst: blastocoele B3 or higher; inner-cell-mass A/B; trophectoderm A/B; and known implantation outcome for each transferred blastocyst. Blastocysts were classified into good-quality and poor-quality embryo groups at day 2 and 3. Implantation (38.7% versus 41.4), clinical pregnancy (40.3% versus 45.9%), miscarriage (22.2% versus 26.7%;) and live birth rates (37.4% versus 38.8%) were comparable in day 2 good and poor-quality embryo groups. No signficiant differences in morphology of transferred blastocysts at day 3 were found. Multivariable analysis highlighted that poor or good embryo quality at day 2 and day 3 were not predictive of the implantation of good-quality blastocysts (at day 2: adjusted odds ratio = 0.82 CI 95% 0.49 to 1.38; at day 3: adjusted odds ratio = 1.39; CI 95% 0.77 to 2.52). Good-quality blastocyst transfer should, therefore, be carried out irrespective of embryo quality at cleavage stage, as it may not compromise success rates in a good-prognosis population., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2013. Published by Elsevier SAS.)

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., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Luteinizing hormone (LH) is an hypophyseal glycoprotein involved in both follicular maturation and corpus luteum function. During the follicular phase, effects of LH must be considered according to the stages of follicular development: in the early follicular phase, LH acts through specific receptors, constitutively present on thecal cells, for stimulating androgen production. Androgens seem to be positively involved in the folliculogenesis in primates. Indeed, a positive correlation has been recently established between androgen receptor expression and follicular cell proliferation. Furthermore, androgens are active through a conversion to estrogens in granulosa cells. Estrogens are needed for achieving pregnancy. Thus, a question remains: what in the minimal amount of endogenous LH required for an optimal production of oestradiol? Several models have been investigated in clinical situations with hypogonadotrophic hypogonadism: WHO type I anovulation or GnRH analog-induced hypogonadisms. A large majority of these studies conclude that the minimal amount of LH needed during the follicular phase is probably low (< 1.5 IU/L of plasma LH level). Recent availability of GnRH antagonist will give a new opportunity for evaluating this minimal LH threshold. During the late follicular phase, LH plays a biphasic role, with a positive effect on steroidogenesis but a negative effect on cell proliferation. As suggested by S. Hillier, this negative effect on cell proliferation may be relevant to control the rate of follicular growth. One study, performed in WHO type I anovulatory patients, seems to confirm this assumption but further evaluation is needed to give support to this concept. Finally, LH is also involved in corpus luteum function. Due to the short half-life of LH as compared to hCG, the role of LH must be evaluated according to the adjunct therapies. For example, following a long-term GnRH aganist administration that constantly induces a profound hypophyseal desensitization, LH administration must be repeated to adequately sustain the corpus luteum function. This conclusion must be reconsidered with the recent introduction of GnRH antagonists. Indeed, according to their short-term effects on LH secretion, it may be presumed that a single injection of LH may be effective to maintain an adequate corpus luteum function.

Unlabelled: Infiltrating leukocyte population appears at the time of implantation in the endometrium of human and other mammals with hemochorial placentation. This leukocyte population is mainly composed of macrophages and typical granular lymphocytes CD56+ CD16-. 63 endometrial samples were studied using immunocytochemistry, before IVF and embryo transfer. We evaluated the sensibility for the assessment of immunological relevant infiltrating cells, of classical histopathologic examination compared with quantitation of leukocyte-common-antigen antibody immunostaining. 21 samples were thoroughly studied during proliferative phase., Results: The sensibility of classical histologic analysis for the semi-quantitative assessment of leukocyte population, even when performed by an experienced histopathologist, is only 62%. When leukocyte population during proliferative phase is dense, it is mainly composed of macrophages and CD56+ CD16- lymphocytes., Conclusion: Immunological reaction already reported around the time of implantation may occur at other period of the menstrual cycle. Close mechanisms of the control and functions of this characteristic reaction remain to clarify.