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Les fausses couches spontanées (FCS) répétées (FCSR) constituent un challenge diagnostique et thérapeutique, avec la moitié des cas inexpliquée par le bilan recommandé et l'absence de consensus thérapeutique. Les aberrations chromosomiques embryonnaires sont une cause majeure de FCS mais la probabilité d'une perte de grossesse aneuploïde tend à diminuer avec le nombre de FCS antérieures. Un déséquilibre des réponses immunitaires maternelles au sein de l'endomètre semble impliqué dans certains cas de FCSR inexpliquées. Cette hypothèse a conduit à l'utilisation empirique de l'hydroxychloroquine (HCQ), reconnue pour ses effets immunomodulateurs et protecteurs vasculaires, dans cette indication malgré l'absence de preuves d'efficacité clinique. Dans cette étude, nous avons examiné les résultats de grossesses exposées à l'HCQ et les facteurs prédictifs de l'évolution de la grossesse au-delà du premier trimestre chez des femmes aux antécédents de FCSR en utilisant les données du registre français FALCO. Le registre FALCO est une étude observationnelle prospective multicentrique française qui inclut des grossesses chez des femmes âgées de 18 à 49 ans aux antécédents de 3 ou plus FCS avant 12 semaines d'aménorrhée (SA) consécutives ou non. Les patientes bénéficient du bilan de FCSR recommandé par l'ESHRE et celles qui répondent aux critères de classification du syndrome des anti-phospholipides ne sont pas incluses dans le registre. Pour cette étude, nous avons inclus toutes les grossesses spontanées du registre FALCO exposées à l'HCQ avant la conception ou au début de la grossesse. Nous avons exclu les grossesses chez les patientes sous HCQ au long terme pour une maladie auto-immune et/ou celles exposées de manière concomitante à une biothérapie, des immunoglobulines et/ou des intralipides intraveineux. Un traitement concomitant par une anti-agrégation plaquettaire (AAP), une héparine de faible poids moléculaire (HBPM) à dose prophylactique et/ou une corticothérapie était autorisé. Le critère d'évaluation principal était une grossesse évolutive au-delà du 1er trimestre (> 12SA). Nous avons analysé 100 grossesses survenues chez 74 femmes. L'âge moyen lors de la conception était de 34,2 (±4,7) ans et le nombre médian de fausses couches antérieures était de 5 [IIQ = 2], avec un maximum de 12. L'HCQ était initiée avant la conception pour 71 (71 %) grossesses (durée médiane de 8,7 semaines) et une fois la grossesse confirmée (< 6SA) pour les 29 (29 %) autres. 78 (78 %) grossesses étaient également exposées à de la prednisone, 56 (56 %) à une AAP et 41 (41 %) à une HBPM. Seules 38 (38 %) grossesses ont évolué au-delà de 12SA. Le risque de présenter une nouvelle FCS précoce augmentait avec le nombre de FCS antérieures, mais pas avec l'âge. Chez les femmes ayant déjà présenté 5 ou 6 FCS (n = 44), 65 % des grossesses se sont arrêtées au premier trimestre, tandis que cette incidence atteignait 92,9 % chez celles ayant eu ≥ 7 FCS antérieures (n = 14). Pour les 21 (21 %) grossesses exposées à l'HCQ pendant plus de trois mois en préconceptionnel, l'incidence de nouvelle FCS précoce n'était pas plus faible que celles exposées pendant une durée plus courte (15/21, 71,4 % vs 28/47, 59,6 % ; p = 0,49). La répartition des anomalies identifiées lors du bilan de FCSR et l'exposition aux autres médicaments n'étaient pas statistiquement différentes entre les grossesses évolutives > 12SA et celles arrêtées ≤ 12SA. L'analyse multivariée a révélé que seul un antécédent de ≤ 4 FCS antérieures était prédictif de la poursuite de la grossesse > 12 SA, après ajustement pour l'âge et la durée d'exposition à l'HCQ avant la conception (OR ajusté = 3,13 [1,31–7,83], p = 0,01). Dans cette cohorte de grossesses chez des femmes aux antécédents de FCSR et exposées à l'HCQ en début de grossesse, le seul facteur déterminant l'évolutivité de ces nouvelles grossesses au-delà du premier trimestre était un nombre peu élevé de FCS antérieures. Ces résultats suggèrent indirectement que l'HCQ ne semble pas améliorer l'issue de la grossesse dans les cas de FCSR susceptibles d'être liées à un déséquilibre immunitaire local. [ABSTRACT FROM AUTHOR]

Research Question: Do women with endometriosis undergoing oocyte retrieval for fertility preservation experience the same level of pain as women undergoing oocyte retrieval for IVF?, Design: This retrospective cohort study included 796 cycles in women with endometriosis undergoing oocyte retrieval for fertility preservation (n = 401) or IVF (n = 395) between January 2020 and October 2022. Post-operative pain assessments were compared between the two groups using a numeric rating scale (NRS)., Results: Women in the fertility preservation group were younger (32.1 ± 4.2 years versus 35.1 ± 4.1 years; P < 0.001), had a lower body mass index (22.8 ± 3.9 kg/m 2 versus 24.6 ± 4.4 kg/m 2 ; P < 0.001) and had a lower concentration of anti-Müllerian hormone (1.8 ± 1.5 ng/ml versus 2.15 ± 2.11 ng/ml; P = 0.026) in comparison with women in the IVF group. The oestrogen concentration on the day of ovulation trigger was higher in women in the fertility preservation group (2188 ± 1152 pg/ml versus 2081 ± 995 pg/ml; P = 0.004), and the prevalence rates of adenomyosis and digestive endometrial lesions were lower in women in the fertility preservation group (14% versus 29%, P < 0.001; 16% versus 25%, P = 0.003, respectively) compared with women in the IVF group. After oocyte puncture, more women in the fertility preservation group had an NRS pain score >3 (moderate to severe pain) compared with women in the IVF group (20% versus 14%; P = 0.018). The progestin-primed ovarian stimulation (PPOS) protocol was identified as an independent predictive factor of greater post-operative pain (adjusted OR 2.30, 95% CI 1.06-5.15; P = 0.039)., Conclusion: Women with endometriosis undergoing fertility preservation reported more intense post-operative pain in the recovery room than women undergoing IVF. The PPOS protocol was an independent risk factor of intense pain (NRS pain score >3) in women with endometriosis, but further studies are needed to confirm this result., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Study Question: What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?, Summary Answer: In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages., What Is Known Already: Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL., Study Design, Size, Duration: The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals., Participants/materials, Setting, Methods: Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth., Main Results and the Role of Chance: One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01)., Limitations, Reasons for Caution: Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered., Wider Implications of the Findings: Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system., Study Funding/competing Interest(s): The research received no specific funding, and the authors declare no competing interests., Trial Registration Number: clinicaltrial.gov NCT05557201., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: To update the 2010 CNGOF clinical practice guidelines for the first-line management of infertile couples., Materials and Methods: Five major themes (first-line assessment of the infertile woman, first-line assessment of the infertile man, prevention of exposure to environmental factors, initial management using ovulation induction regimens, first-line reproductive surgery) were identified, enabling 28 questions to be formulated using the Patients, Intervention, Comparison, Outcome (PICO) format. Each question was addressed by a working group that had carried out a systematic review of the literature since 2010, and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) methodology to assess the quality of the scientific data on which the recommendations were based. These recommendations were then validated during a national review by 40 national experts., Results: The fertility work-up is recommended to be prescribed according to the woman's age: after one year of infertility before the age of 35 and after 6months after the age of 35. A couple's initial infertility work-up includes a single 3D ultrasound scan with antral follicle count, assessment of tubal permeability by hysterography or HyFOSy, anti-Mullerian hormone assay prior to assisted reproduction, and vaginal swabbing for vaginosis. If the 3D ultrasound is normal, hysterosonography and diagnostic hysteroscopy are not recommended as first-line procedures. Chlamydia trachomatis serology does not have the necessary performance to predict tubal patency. Post-coital testing is no longer recommended. In men, spermogram, spermocytogram and spermoculture are recommended as first-line tests. If the spermogram is normal, it is not recommended to check the spermogram. If the spermogram is abnormal, an examination by an andrologist, an ultrasound scan of the testicles and hormonal test are recommended. Based on the data in the literature, we are unable to recommend a BMI threshold for women that would contraindicate medical management of infertility. A well-balanced Mediterranean-style diet, physical activity and the cessation of smoking and cannabis are recommended for infertile couples. For fertility concern, it is recommended to limit alcohol consumption to less than 5 glasses a week. If the infertility work-up reveals no abnormalities, ovulation induction is not recommended for normo-ovulatory women. If intrauterine insemination is indicated based on an abnormal infertility work-up, gonadotropin stimulation and ovulation monitoring are recommended to avoid multiple pregnancies. If the infertility work-up reveals no abnormality, laparoscopy is probably recommended before the age of 30 to increase natural pregnancy rates. In the case of hydrosalpinx, surgical management is recommended prior to ART, with either salpingotomy or salpingectomy depending on the tubal score. It is recommended to operate on polyps>10mm, myomas 0, 1, 2 and synechiae prior to ART. The data in the literature do not allow us to systematically recommend asymptomatic uterine septa and isthmoceles as first-line surgery., Conclusion: Based on strong agreement between experts, we have been able to formulate updated recommendations in 28 areas concerning the initial management of infertile couples., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The evolution of medical techniques as well as legislative changes currently allow to propose fertility preservation strategies in the context of transidentity. During "female to male" transition, androgen therapy has an impact on gonadal function since it usually induces a blockage of ovulation with amenorrhea. Although this effect is reversible when treatment is stopped, the possible long-term effects of testosterone treatment on future fertility or health of future children are poorly known. In addition, transitional surgeries definitely compromise fecundity when they include bilateral ovariectomy and/or hysterectomy. Yet, although long ignored or poorly expressed, the desire for parenthood is a reality in transgender men. Fertility preservation options in FtM transition rely on oocyte or ovarian tissue cryopreservation. The purpose of this review is to provide an overview of the literature regarding fertility preservation in transgender men. Although series remain limited, the increase in the number of recently published articles reflects the interest in improving the management of fertility issues in transgender men., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Research Question: Can a machine learning model better predict the cumulative live birth rate for a couple after intrauterine insemination or embryo transfer than Cox regression based on their personal characteristics?, Study Design: Retrospective cohort study conducted in two French infertility centres (Créteil and Tenon Hospitals) between 2012 and 2019, including 1819 and 1226 couples at Créteil and Tenon, respectively. Two models were applied: a Cox regression, which is almost exclusively used in assisted reproductive technology (ART) predictive modelling, and a tree ensemble-based model using XGBoost implementation. Internal validations were performed on each hospital dataset separately; an external validation was then carried out on the Tenon Hospital's population., Results: The two populations were significantly different, with Tenon having more severe cases than Créteil, although internal validations show comparable results (C-index of 60% for both populations). As for the external validation, the XGBoost model stands out as being more stable than Cox regression, with the latter having a higher performance loss (C-index of 60% and 58%, respectively). The explicability method indicates that the XGBoost model relies strongly on features such as the ages of a couple, causes of infertility, and the woman's body mass index or infertility duration, which is consistent with the ART literature about risk factors., Conclusions: Overall performances are still relatively modest, which is coherent with all reported ART predictive models. Explicability-based methods would allow access to new knowledge, to gain a greater comprehension of which characteristics and interactions really influence a couple's journey. These models can be used by practitioners and patients to make better informed decisions about performing ART., (Copyright © 2022. Published by Elsevier Ltd.)

Results from studies reporting the optimal stimulation duration of IVF-ICSI cycles are inconsistent. The aim of this study was to determine whether, in the presence of early ovulation-triggering criteria, prolonged ovarian stimulation modified the chances of a live birth. This cross-sectional study included 312 women presenting triggering criteria beginning from D8 of ovarian stimulation. Among the 312 women included in the study, 135 were triggered for ovulation before D9 (D ≤ nine group) and 177 after D9 (D > nine group). The issues of fresh +/− frozen embryo transfers were taken into consideration. Cumulative clinical pregnancy and live-birth rates after fresh +/− frozen embryo transfers were similar in both groups (37% versus 46.9%, p = 0.10 and 19.3% versus 28.2%, p = 0.09, respectively). No patient characteristics were found to be predictive of a live birth depending on the day of ovulation trigger. Postponing of ovulation trigger did not impact pregnancy or live-birth rates in early responders. A patient’s clinical characteristics should not influence the decision process of ovulation trigger day in early responders. Further prospective studies should be conducted to support these findings.

Objectives: To provide clinical practice guidelines about fertility preservation (FP) for women with benign gynecologic disease (BGD) developed by a modified Delphi consensus process for oocyte vitrification in women with benign gynecologic disease., Methods: A steering committee composed of 14 healthcare professionals and a patient representative with lived experience of endometriosis identified 42 potential practices related to FP for BGD. Then 114 key stakeholders including various healthcare professionals (n=108) and patient representatives (n=6) were asked to participate in a modified Delphi process via two online survey rounds from February to September 2020 and a final meeting. Due to the COVID-19 pandemic, this final meeting to reach consensus was held as a videoconference in November 2020., Results: Survey response of stakeholders was 75 % (86/114) for round 1 and 87 % (75/86) for round 2. Consensus was reached for the recommendations for 28 items, that have been distributed into five general categories: (i) Information to provide to women of reproductive age with a BGD, (ii) Technical aspects of FP for BGD, (iii) Indications for FP in endometriosis, (iv) Indications for FP for non-endometriosis BGD, (v) Indications for FP after a fortuitous diagnosis of an idiopathic diminished ovarian reserve., Conclusion: These guidelines provide some practice advice to help health professionals better inform women about the possibilities of cryopreserving their oocytes prior to the management of a BGD that may affect their ovarian reserve and fertility., Study Funding/competing Interest(s): The CNGOF (Collège National des Gynécologues Obstétriciens Français) funded the implementation of the Delphi process., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Introduction: Up to 30% of couples may face secondary infertility. The impact of ectopic pregnancy, spontaneous abortion, pregnancy termination or live birth with caesarean section may impair further fertility in different ways. However, secondary infertility after physiological vaginal life childbirth has been little studied. The aim of this study was to describe the population and the fertility issues and analyze the predictive factors of success in in vitro fertilization in women presenting secondary infertility after a physiological vaginal childbirth., Material and Methods: This single-centre retrospective study included women aged 18-43 years consulting between 2013 and 2020 for secondary infertility in a couple having already had previous vaginal life childbirth. Couples' characteristics, management decision after the first consultation and IVF outcomes were analyzed., Results: Secondary infertility was found in 286 couples, out of whom 138 had a history of vaginal life childbirth. Population was characterized by an advanced female age and overweight. After the first consultation, IVF was performed in only 40% of couples. No predictive factor of live birth was found., Conclusion: Our study shows that in couples with secondary infertility after prior physiological delivery cigarette smoking is frequent in male partners, and ovarian reserve markers are altered. However, no statistically significant predictive factor of live birth after IVF treatment has been identified. Further large prospective studies are necessary., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Research Question: Does mild COVID-19 infection affect the ovarian reserve of women undergoing an assisted reproductive technology (ART) protocol?, Design: A prospective observational study was conducted between June and December 2020 at the ART unit of Tenon Hospital, Paris. Women managed at the unit for fertility issues by in-vitro fecundation, intracytoplasmic sperm injection (IVF/ICSI), fertility preservation, frozen embryo transfer or artificial insemination, and with an anti-Müllerian hormone (AMH) test carried out within 12 months preceding ART treatment, were included. All the women underwent a COVID rapid detection test (RDT) and AMH concentrations between those who tested positive (RDT positive) and those who tested negative (RDT negative)., Results: The study population consisted of 118 women, 11.9% (14/118) of whom were COVID RDT positive. None of the tested women presented with a history of severe COVID-19 infection. The difference between the initial AMH concentration and AMH concentration tested during ART treatment was not significantly different between the COVID RDT positive group and COVID RDT negative group (-1.33 ng/ml [-0.35 to -1.61) versus -0.59 ng/ml [-0.15 to -1.11], P = 0.22)., Conclusion: A history of mild COVID-19 infection does not seem to alter the ovarian reserve as evaluated by AMH concentrations. Although these results are reassuring, further studies are necessary to assess the effect of COVID-19 on pregnancy outcomes in women undergoing ART., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

International guidelines are published to provide standardized information and fertility preservation (FP) care for adults and children. The purpose of the study was to conduct a modified Delphi process for generating FP guidelines for BGD. A steering committee identified 42 potential FP practices for BGD. Then 114 key stakeholders were asked to participate in a modified Delphi process via two online survey rounds and a final meeting. Consensus was reached for 28 items. Among them, stakeholders rated age-specific information concerning the risk of diminished ovarian reserve after surgery as important but rejected proposals setting various upper and lower age limits for FP. All women should be informed about the benefit/risk balance of oocyte vitrification-in particular about the likelihood of live birth according to age. FP should not be offered in rASRM stages I and II endometriosis without endometriomas. These guidelines could be useful for gynecologists to identify situations at risk of infertility and to better inform women with BGDs who might need personalized counseling for FP.

Introduction: Recurrent miscarriages are defined as three or more early miscarriages before 12 weeks of gestation. The aim of this study was to describe a cohort of women with unexplained recurrent miscarriages, evaluate several potential biomarkers of immune origin, and describe the outcome of pregnancies under immunomodulatory therapies., Methods: Women having a history of at least 3 early miscarriages without any etiology were recruited from 3 university hospitals., Results: Among 101 women with recurrent miscarriages, overall, 652 pregnancies have been included in the analysis. Women which experienced miscarriages were older (33.3 ± 5.4 versus 31.9 ± 6.7; p = 0.03), with history of more pregnancies (4 (2-6) versus 3.5 (1-5.75); p 0.0008), and less frequently the same partner (406 (74%) versus 79 (86%); p=0.01). There was no difference in the level and frequencies of biomarkers of immune origin (NK, lymphocyte, gamma globulins and blood cytokine levels and endometrial uNK activation status), except the higher rates of positive antinuclear antibodies in women with live birth (12 (13%) versus 36 (7%); p=0.03). Among the 652 pregnancies, 215 (33%) have been treated and received either aspirin/low weighted molecular heparin (LMWH) and/or combined to different lines of immunomodulatory treatment. Patients with pregnancy under treatment had a significantly higher rate of cumulative live birth rate than those with untreated ones (43.0% vs 34.8%; p = 0.04). When compared to patients with untreated pregnancies, patients with steroids during the pregnancy had twice more chances to obtain live birth (OR 2.0, CI95% 1.1 - 3.7, p = 0.02)., Conclusions: Unexplained recurrent miscarriages could have improved obstetrical outcome under immunomodulatory therapies and in particular steroids., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Recurrent implantation failure is defined as the absence of pregnancy after at least three transfers of good-quality embryos after in vitro fecundation/intracytoplasic sperm injection., Aim: The aim of this study was to describe a multicentre cohort of women with unexplained RIF, to analyse the factors associated with clinical pregnancy and to evaluate the immunomodulatory therapies efficacy., Methods: Women were consecutively recruited from university departments with unexplained RIF., Results: Sixty-four women were enrolled with mean age 36 ± 3 years. The rates of clinical pregnancy in 64 women were compared in untreated and treated cycles and according to therapies used during the last prospectively followed embryo transfer. A clinical pregnancy after the transfer was noted in 56 % pregnancies on intralipids and in 50 % on prednisone, versus 5 % in untreated ones (p < 0.001). The 340 embryo transfers of these 64 women resulted in 68 clinical pregnancies and 18 live births. Clinical pregnancies were significantly more frequent in treated versus untreated embryo transfers (44 % vs 9 %; p < 0.001) with odds ratio at 8.13 (95 % CI 4.49-14.72, p < 0.0001). Cumulative pregnancy rates were higher for steroid-treated transfers than for untreated transfers when considering overall transfers before and after using steroids and also only those under steroids. Cumulative pregnancy rates were not different from steroid- and intralipid-treated embryo transfers CONCLUSIONS: In this multicentre study of women with unexplained RIF, use of immunomodulatory treatments before embryo transfer resulted in higher clinical pregnancy. Randomised, well-designed studies in well-defined population of RIF women are necessary to confirm our preliminary data., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dietary supplementation is commonly used in men with male infertility but its exact role is poorly understood. The aim of this multicenter, randomized, double-blind, placebo-controlled trial was to evaluate the impact of high-dose folic acid supplementation on IVF-ICSI outcomes. 162 couples with male infertility and an indication for IVF-ICSI were included for one IVF-ICSI cycle. Male partners of couples wishing to conceive, aged 18-60 years old, with at least one abnormal spermatic criterion were randomized in a 1:1 ratio to receive daily supplements containing 15 mg of folic acid or a placebo for 3 months from Day 0 until semen collection for IVF-ICSI. Sperm parameters and DNA fragmentation before and after the treatment and the biochemical and clinical pregnancy rates after the fresh embryo transfer were analyzed. We observed an increase in the biochemical pregnancy rate and a trend for a higher clinical pregnancy rate in the folic acid group compared to placebo (44.1% versus 22.4%, p = 0.01 and 35.6% versus 20.4%, p = 0.082, respectively). Even if no changes in sperm characteristics were observed, a decrease in DNA fragmentation in the folic acid group was noted (8.5 ± 4.5 vs. 6.4 ± 4.6, p < 0.0001). High-dose folic acid supplementation in men requiring IVF-ICSI for male infertility improves IVF-ICSI outcomes.

Purpose: A protective effect of anti-Müllerian hormone (AMH) on follicle atresia was recently demonstrated using long-term treatments, but this effect has never been supported by mechanistic studies. This work aimed to gain an insight into the mechanism of action of AMH on follicle atresia and on how this could account for the increased follicle pool observed in women with polycystic ovary syndrome (PCOS)., Methods: In vivo and in vitro experiments were performed to study the effects of AMH on follicle atresia and on the proliferation and apoptosis of granulosa cells (GCs). RNA-sequencing was carried out to identify new AMH target genes in GCs. The expression of some of these genes in GCs from control and PCOS women was compared using microfluidic real time quantitative RT-PCR., Results: A short-term AMH treatment prevented follicle atresia in prepubertal mice. Consistent with this result, AMH inhibited apoptosis and promoted proliferation of different models of GCs. Moreover, integrative biology analyses of 965 AMH target genes identified in 1 of these GC models, confirmed that AMH had initiated a gene expression program favoring cell survival and proliferation. Finally, on 43 genes selected among the most up- and down-regulated AMH targets, 8 were up-regulated in GCs isolated from PCOS women, of which 5 are involved in cell survival., Main Conclusions: Our results provide for the first time cellular and molecular evidence that AMH protects follicles from atresia by controlling GC survival and suggest that AMH could participate in the increased follicle pool of PCOS patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Polycystic ovary syndrome (PCOS) is characterized by an oligo-anovulation, hyperandrogenism and polycystic ovarian morphology combined with major metabolic disturbances. However, despite the high prevalence and the human and economic consequences of this syndrome, its etiology remains unknown. In this study, we show that female Goto-Kakizaki (GK) rats, a type 2 diabetes mellitus model, encapsulate naturally all the reproductive and metabolic hallmarks of lean women with PCOS at puberty and in adulthood. The analysis of their gestation and of their fetuses demonstrates that this PCOS-like phenotype is developmentally programmed. GK rats also develop features of ovarian hyperstimulation syndrome. Lastly, a comparison between GK rats and a cohort of women with PCOS reveals a similar reproductive signature. Thus, this spontaneous rodent model of PCOS represents an original tool for the identification of the mechanisms involved in its pathogenesis and for the development of novel strategies for its treatment.

The incidence (rate per 100 000) of borderline ovarian tumors (BOTs) increases progressively with age, starting at 15-19 years and peaking at around 4.5 cases per 100 000 at an age of 55-59 years (LE3) with a median age of 46 years. The five year survival for FIGO stages I, II, III and IV is 99.7 % (95 % CI: 96.2-100 %), 99.6 % (95 % CI: 92.6-100 %), 95.3 % (95 % CI: 91.8-97.4 %) and 77.1 % (95 % CI: 58.0-88.3 %), respectively (LE3). An epidemiological association exists between the individual risk of BOT and family history of BOT and certain other cancers (pancreatic, lung, bone, leukemia) (LE3), a personal history of benign ovarian cyst (LE2), a personal history of tubo-ovarian infection (LE3), the use of a levonorgestrel intrauterine device (LE3), oral contraceptive use (LE3), multiparity (LE3), Hormonal replacement therapy (LE3), high consumption of Coumestrol (LE4), medical treatment for infertility with progesterone (LE3) and non-steroidal anti-inflammatory drug use (LE3). Screening for BOTs is not recommended for patients (Grade C). The overall risk of recurrence of BOTs varies between 2% and 24 %, with an overall survival greater than 94 % at 10 years, and the risk of an invasive recurrence of a BOT ranges from 0.5 % to 3.8 %. The use of scores and nomograms can be useful in assessing the risk of recurrence, and providing patients with information (Grade C). The WHO classification is recommended for classifying BOTs. It is recommended that the presence of a microinvasive focus (<5 mm) and microinvasive carcinoma (<5 mm with an atypical nuclei and a desmoplastic stroma reaction) within a BOT be reported. In cases of serous BOT, it is recommended to specify the classic histological subtype or micropapillary / cribriform type (Grade C). When confronted with a BOT, it is recommended that the invasive or non-invasive nature of peritoneal implants can be investigated based solely on the invasion and destruction of underlying adipose or peritoneal tissue which has a desmoplastic stromal reaction where in contact with the invasive clusters (Grade B). For bilateral mucinous BOTs and / or in cases with peritoneal implants or peritoneal pseudomyxoma, it is recommended to also look for a primitive digestive or pancreato-biliary cancer (Grade C). It is recommended to sample ovarian tumors suspected of being BOTs by focusing samples on vegetations and solid components, with at least 1 sample per cm in tumors with a size less than 10 cm and 2 samples per cm in tumors with a size greater than 10 cm (Grade C). In cases of BOTs and in the absence of macroscopic omental involvement after careful macroscopic examination, it is recommended to perform at least 4-6 systematic sampling blocks and to include all peritoneal implants (Grade C). It is recommended to consult an expert pathologist in gynecology when a BOT suspicion requires intraoperative extemporaneous histology (grade C). Endo-vaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended that a pelvic MRI be performed (Grade A). To analyze an adnexal mass with MRI, it is recommended to use an MRI protocol with T2, T1, T1 Fat Sat, dynamic and diffusion sequences as well as gadolinium injection (Grade B). To characterize an adnexal mass with MRI, it is recommended to include a score system for malignancy (ADNEX MR/O-RADS) (Grade C) in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being a BOT (Grade C). Macroscopic MRI features should be analyzed to differentiate BOT subtypes (Grade C). Pelvic ultrasound is the first-line examination for the detection and characterization of adnexal masses during pregnancy (Grade C). Pelvic MRI is recommended from 12 weeks of gestation in case of an indeterminate adnexal mass and should provide a diagnostic score (Grade C). Gadolinium injection must be minimized as fetal impairment has been proven (Grade C). It is recommended that serum levels of HE4 and CA125 be evaluated and that the ROMA score for the diagnosis of an indeterminate ovarian mass on imaging be used (grade A). In case of suspicion of a mucinous BOT on imaging, dosage of serum levels of CA 19-9 can be considered (Grade C). If the determination of tumor markers is normal preoperatively, routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of preoperative elevation in tumor markers, the determination of serum CA 125 levels is recommended in the follow-up of BOT (Grade B). When conservative treatment of a BOT has been adopted, the use of endovaginal and transabdominal ultrasonography is recommended during follow-up (Grade B)., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: The management of endometriosis-related infertility is still under debate. The Endometriosis Fertility Index (EFI) score is performant to predict the occurrence of a spontaneous pregnancy following surgery, but was not evaluated in a cost-effectiveness perspective. Our objective was to quantify fertility outcomes, and costs of different care pathways for endometriosis-associated infertility after primary surgery, with a stratification on the EFI score., Study Design: We conducted a cost-effectiveness analysis based on a decision-tree model in a Tertiary-care university hospital. Extracted form a prospectively maintained database, 608 patients with endometriosis-associated infertility, who underwent laparoscopic treatment with an evaluation of the EFI score, were discriminated between different strategies: natural conception, immediate IVF-ICSI, delayed IVF-ICSI. The pregnancy rate and the live birth rate were the effectiveness outcomes. We considered direct and indirect costs in each strategies. The analysis was stratified according to the EFI score., Results: After surgery, 163 women with immediate IVF-ICSI (strategy I) were compared with 445 women who had natural conception attempts during a year (strategy II). After a year failure of natural conception attempts, 133 women continuing natural conception attempts (strategy III) were compared with 168 women who had delayed IVF-ICSI (strategy IV). The respective PR and LBR were 62.6 % and 52.1 % for strategy I, and 32.4 % and 23.8 % for strategy II. Compared to strategy II, strategy I was more costly and more effective (Incremental Cost Effectiveness Ratio (ICER): 31,469 €/pregnancy and 33,568 €/live birth)). No added benefit was observed for patients in strategy I with an EFI score [0-3] after two IVF-ICSI cycles. Strategy III was strongly dominant versus strategy IV for patients with an EFI score [9-10]. Compared to strategy III, strategy VI was more costly and more effective (ICER: 79,674 €/pregnancy, 53,188 €/pregnancy and 27,748 €/pregnancy respectively for patients with an EFI score [7-8], [4-6] and [0-3])., Conclusion: Immediate IVF-ICSI after surgery is effective but associated with substantial costs for the healthcare system. Taking into account healthcare costs, the EFI is a useful score for helping a couple decide between different care pathways -natural conception, immediate or delayed IVF-ICSI- after surgery for endometriosis-associated infertility., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Borderline ovarian tumours (BOT) represent around 15% of all ovarian neoplasms and are more likely to be diagnosed in women of reproductive age. Overall, given the epidemiological profile of BOT and their favourable prognosis, ovarian function and fertility preservation should be systematically considered in patients presenting these lesions., Methods: The research strategy was based on the following terms: borderline ovarian tumour, fertility, fertility preservation, infertility, fertility-sparing surgery, in vitro fertilization, ovarian stimulation, oocyte cryopreservation, using PubMed, in English and French., Results and Conclusions: Fertility counselling should become an integral part of the clinical management of women with BOT. Patients with BOT should be informed that surgical management of BOT may cause damage ovarian reserve and/or peritoneal adhesions. Nomogram to predict recurrence, ovarian reserve markers and fertility explorations should be used to provide a clear and relevant information about the risk of infertility in patients with BOT. Fertility-sparing surgery should be considered for young women who wish preserving their fertility when possible. There is insufficient evidence to claim a causal relation between controlled ovarian stimulation (COS) and BOT. However, in case of poor prognosis factors, the use of COS should be considered cautiously through a multidisciplinary approach. In case of infertility after surgery for BOT, COS can be performed without delay, once histopathological diagnosis of BOT is confirmed. There is insufficient consistent evidence that fertility drugs and COS increase the risk of recurrence of BOT after conservative management. The conservative surgical treatment can be associated to oocyte cryopreservation considering the high risk of recurrence of the disease. In women with BOT recurrence in a single ovary and in women with bilateral ovarian involvement when the conservative management is not possible, other fertility preservation strategies are available, but still experimental., (Copyright © 2020. Published by Elsevier Masson SAS.)

This work was carried out under the aegis of the CNGOF (Collège national des gynécologues et obstétriciens français) and proposes guidelines based on the evidence available in the literature. The objective was to define the diagnostic and surgical management strategy, the fertility preservation and surveillance strategy in Borderline Ovarian Tumor (BOT). No screening modality can be proposed in the general population. An expert pathological review is recommended in case of doubt concerning the borderline nature, the histological subtype, the invasive nature of the implant, for all micropapillary/cribriform serous BOT or in the presence of peritoneal implants, and for all mucinous or clear cell tumors (grade C). Macroscopic MRI analysis should be performed to differentiate the different subtypes of BOT: serous, seromucinous and mucinous (intestinal type) (grade C). If preoperative biomarkers are normal, follow up of biomarkers is not recommended (grade C). In cases of bilateral early serous BOT with a desire to preserve fertility and/or endocrine function, it is recommended to perform a bilateral cystectomy if possible (grade B). In case of early mucinous BOT, with a desire to preserve fertility and/or endocrine function, it is recommended to perform a unilateral adnexectomy (grade C). Secondary surgical staging is recommended in case of serous BOT with micropapillary appearance and uncomplete inspection of the abdominal cavity during initial surgery (grade C). For early-stage serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (grade C). Follow up after BOT must be pursued for more than 5 years (grade B). Conservative treatment involving at least the conservation of the uterus and a fragment of the ovary in a patient wishing to conceive may be proposed in advanced stages of BOT (grade C). A new surgical treatment that preserves fertility after a first non-invasive recurrence may be proposed in women of childbearing age (grade C). It is recommended to offer a specialized consultation for Reproductive Medicine when diagnosing BOT in a woman of childbearing age. Hormonal contraceptive use after serous or mucinous BOT is not contraindicated (grade C)., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: PPOS protocols, initially described for FP in women with cancer, have many advantages compared to antagonist protocols. PPOS protocols were not evaluated for women with endometriosis. The objective of the study was to describe fertility preservation outcomes in women with endometriosis and to compare an antagonist protocol with a Progestin-Primed Ovarian Stimulation (PPOS) protocol., Method: We conducted a prospective cohort study associated with a cost-effectiveness analysis in a tertiary-care university hospital. The measured outcomes included the numbers of retrieved and vitrified oocytes, and direct medical costs. In the whole population, unique and multiple linear regressions analysis were performed to search for a correlation between individual characteristics and the number of retrieved oocyte., Results: We included 108 women with endometriosis who had a single stimulation cycle performed with either an antagonist or a PPOS protocol. Overall, 8.1 ± 6.6 oocytes were retrieved and 6.4 ± 5.6 oocytes vitrified per patient. In the multiple regression model, age (p = 0.001), prior ovarian surgery (p = 0.035), and anti-Mullerian hormone level (p = 0.001) were associated with the number of retrieved oocytes. Fifty-four women were stimulated with an antagonist protocol, and 54 with a PPOS protocol. A mean of 7.9 ± 7.4 oocytes were retrieved in the antagonist group and 8.2 ± 5.6 in the PPOS group (p = 0.78). A mean of 6.4 ± 6.4 oocytes were vitrified in the antagonist group and 6.4 ± 4.7 in the PPOS group (p = 1). In the cost-effectiveness analysis, the PPOS protocol was strongly dominant over the antagonist protocol., Conclusion: Fertility preservation procedures are feasible and effective for patients affected by endometriosis. Antagonist and PPOS protocols were associated with similar results but the medico-economic analysis was in favor of PPOS protocols.

Objective: Endometriosis affects 10% of women in reproductive age and alters fertility. Its management is still debated notably the timing of surgery and ART in infertility. Several tools have been created to guide the practitioner and the couple yet many limitations persist. The objective is to create a nomogram to predict the likelihood of a live birth after surgery followed by assisted reproductive technology (ART) for patients with endometriosis-related infertility., Study Design: All women in a public university hospital who attempted to conceive by ART after surgery for endometriosis-related infertility from 2004 to 2016 were included. We created a model using multivariable linear regression based on a retrospective database., Result: Of the 297 women included, 171 (57.6%) obtained a live birth. Age, duration of infertility, number of ICSI-IVF cycles, ovarian reserve and the revised American Fertility Society (rAFS) score were included in the nomogram. The predictive model had an area under the curve (AUC) of 0.77 (95% CI, 0.75-0.79) and was well calibrated. The external validation of the model was achieved with an AUC of 0.71 (95% CI, 0.69-0.73) and calibration was good. The staging accuracy according to AUC criteria for the nomogram compared to the currently used Endometriosis Infertility Index to predict live births were 0.77 (95% CI, 0.75-0.79) and 0.60 (95% CI: 0.57-0.63), respectively., Conclusion: This simple tool appears to accurately predict the likelihood of a live birth for a patient undergoing ART after surgery for endometriosis-related infertility. It could be used to counsel patients in their choice between spontaneous versus ART conception, or oocyte donation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We aimed to compare the proportion of peripheral blood natural killer (NK) cells (CD3 - CD56 + ) and T-cell large granular lymphocytes (CD8 + CD57 + ) during preconception in a homogenous group of women with unexplained well-defined recurrent miscarriage (RM) and repeated implantation failure (RIF) vs healthy controls in relation to pregnancy outcomes. This case-control study followed by a literature review and meta-analysis was conducted in three university hospitals. Patients and controls were consecutively recruited from December 2015 to October 2017. In total, 115 women were included in the study: 54 with RM, 41 with RIF and 20 healthy controls with ≥ 2 term births. Percentages of CD3 - CD56 + and CD8 + CD57 + cells and sub-populations of CD3 - CD56 + cells did not differ between cases and controls. The results for women with subsequent miscarriage did not differ from those with live births. The meta-analysis of the literature showed higher NK-cell proportions in RM [mean difference 3.47 (95% CI 2.94-4.00); p < 0.001] and RIF [mean difference 1.64 (95% CI 0.82-2.45); p < 0.001] than controls. However, the heterogeneity between the different studies was high. The proportion of peripheral blood CD3 - CD56 + and CD8 + CD57 + cells in the preconception period does not reflect the risk of implantation failure or miscarriage and should not be recommended indicators for the management of RM and RIF. Further prospective large studies are needed to develop a reliable peripheral blood marker of immune deregulation.

Objective: To study the fertility and live birth (LB) rate in women after surgery for deep infiltrating endometriosis (DIE) without bowel involvement and to evaluate the predictive factors of LB after DIE surgery without bowel involvement., Study Design: Retrospective cohort study. A total of 118 women who wished to conceive and who underwent surgery for DIE without bowel involvement were analyzed between January 2006 and December 2014. A multivariate logistic regression analysis of selected factors and a nomogram to predict the subsequent LB rate was constructed., Results: Thirty-six woman had a LB (30.5%). In multivariate analysis, factors associated with a LB were: age ≤30 years (p = 0.0024), BMI ≤ 25 kg/m 2 (p = 0.029) and Enzian grade 1 (p < 0.001). These factors were associated to develop a nomogram. Before and after the bootstrap sampling procedure, the predictive model had an AUC of 0.84 (95% CI, 0.82-0.86) and 0.81 (95% CI, 0.79-83), respectively, and showed a good calibration., Conclusions: This work presents the originality of describing the fertility and the LB rate after surgery for DIE without bowel involvement with a predictive model. Such tools can help clinicians to support the patient in making an informed decision about fertility treatment options, contributing to the decision-making process by defining simple risk factors of poor LB probability that can help identify good candidates for MAR., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: This study aimed to assess the application of the French guidelines for pregnancies in Turner syndrome (TS) and their impact on perinatal prognosis., Study Design: We performed a French multi-center retrospective study (14 centers), including TS pregnant patients (spontaneously or by Assisted Reproductive Technology (ART)) between January 2006 and July 2017. Only clinical pregnancies were analyzed. The adjustment of medical follow-up modalities to French guidelines was evaluated for all pregnancies after 2009. Pregnancies from oocyte donation (OD) after 2009 were compared to those of a cohort of TS pregnancies obtained by OD before 2009, which were reported by the French Study Group for Oocyte Donation., Results: One hundred seventy pregnancies in 103 patients were included: 35 spontaneous, 5 by means of intra-conjugal ART, and 130 with OD. No serious maternal complications were observed. We reported two stillbirths and one intra uterine fetal death. The French guidelines were partially respected. The preconceptional assessment was carried out in 74% of cases. Cardiology follow-up during pregnancy was performed in accordance with guidelines in 74% of patients. Postpartum cardiac ultrasonography was performed in 45% of pregnancies but only in 11% within 8 days post-partum. When compared to the 2009 historical cohort, the rates of high blood pressure (19% vs. 38%; p < 0.005) pre-eclampsia (8% vs. 21%; p < 0.005) and prematurity <35 weeks (15% vs 38%; p < 0.0001) were lower., Conclusions: The implementation of guidelines has allowed the standardization of TS pregnancy care and improved perinatal indicators for both mothers and children. However, an effort must be done, in a postpartum survey., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Deeply infiltrating endometriosis is a severe form of the disease, defined by endometriotic tissue peritoneal infiltration. The disease may involve the rectovaginal septum, uterosacral ligaments, digestive tract or bladder. Deeply infiltrating endometriosis is responsible for disabling pain and infertility. The purpose of these recommendations is to answer the following question: in case of deeply infiltrating endometriosis associated infertility, what is the best therapeutic strategy? First-line surgery and then in vitro fertilization (IVF) in case of persistent infertility or first-line IVF, without surgery? After exhaustive literature analysis, we suggest the following recommendations: studies focusing on spontaneous fertility of infertile patients with deeply infiltrating endometriosis found spontaneous pregnancy rates about 10%. Treatment should be considered in infertile women with deeply infiltrating endometriosis when they wish to conceive. First-line IVF is a good option in case of no operated deeply infiltrating endometriosis associated infertility. Pregnancy rates (spontaneous and following assisted reproductive techniques) after surgery (deep lesions without colorectal involvement) varie from 40 to 85%. After colorectal endometriosis resection, pregnancy rates vary from 47 to 59%. The studies comparing the pregnancy rates after IVF, whether or not preceded by surgery, are contradictory and do not allow, to date, to conclude on the interest of any surgical management of deep lesions before IVF. In case of alteration of ovarian reserve parameters (age, AMH, antral follicle count), there is no argument to recommend first-line surgery or IVF. The study of the literature does not identify any prognostic factors, allowing to chose between surgical management or IVF. The use of IVF in the indication "deep infiltrating endometriosis" allows satisfactory pregnancy rates without significant risk, regarding disease progression or oocyte retrieval procedure morbidity., (Copyright © 2018. Published by Elsevier Masson SAS.)

Deep infiltrating endometriosis is the most severe form of the disease, defined by infiltration beneath the peritoneum greater than 5mm. It affects several anatomical locations including the bladder, the vesico-uterine cul-de-sac, the torus uterinum, the uterosacral ligament, rectovaginal septum and the colon-rectum. Deep infiltrating endometriosis is associated with infertility. Surgery performed for deep infiltrating endometriosis in the context of pain offers good pregnancy rates either spontaneously or after assisted reproductive technologies. The results are less favorable when digestive tract is involved. IVF performed in the context of deep infiltrating endometriosis allows very satisfactory results and does not entail risks of aggravation of the pathology. There is currently no clear evidence to support either IVF or surgery to manage infertility associated with deep infiltrating endometriosis, but patients should be informed, although a risk of severe complication exists, that surgery is the only way to increase the chances of spontaneous fertility., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: To compare the impact of first-line assisted reproductive technology (ART; intracytoplasmic sperm injection [ICSI]-IVF) and first-line colorectal surgery followed by ART on fertility outcomes in women with colorectal endometriosis-associated infertility., Design: Retrospective matched cohort study using propensity score (PS) matching (PSM) analysis., Setting: University referral centers., Patient(s): A total of 110 women were analyzed from January 2005 to June 2014. A PSM was generated using a logistic regression model based on the age, antimüllerian hormone (AMH) serum level, and presence of adenomyosis to compare the treatment strategy., Intervention(s): First-line surgery group followed by ART versus exclusive ART with in situ colorectal endometriosis., Main Outcome Measure(s): After PSM, pregnancy rates (PRs), live-birth rates (LBRs), and cumulative rates (CRs) were estimated., Result(s): After PSM, in the whole population, the total LBR and PR were 35.4% (39/110) and 49% (54/110), respectively. The specific cumulative LBR at the first ICSI-IVF cycle in the first-line surgery group compared with the first-line ART was, respectively, 32.7% versus 13.0%; at the second cycle, 58.9% versus 24.8%; and at the third cycle, 70.6% versus 54.9%. The cumulative LBRs were significantly higher for women who underwent first-line surgery followed by ART compared with first-line ART in the subset of women with good prognosis (age ≤ 35 years and AMH ≥ 2 ng/mL and no adenomyosis) and women with AMH serum level < 2 ng/mL., Conclusion(s): First-line surgery may be a good option for women with colorectal endometriosis-associated infertility., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: There is no consensual definition of diminished ovarian reserve and the best therapeutic strategy has not yet been demonstrated., Methods: We performed a retrospective study to evaluate outcomes following a first in-vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycle in young women with diminished ovarian reserve. Women with tubal factor, endometriosis or previous stimulation cycle were excluded. We defined diminished ovarian reserve as women ≤38 years with an AMH ≤1.1 ng/mL or antral follicular count ≤7., Results: Among 59 IVF/ICSI cycles (40% IVF/60% ICSI), the pregnancy rate was 17% (10/59) and live birth rate 8.5% (5/59). Miscarriage rate was 50%. Baseline characteristics and IVF outcomes of the pregnant and not pregnant women were compared. No differences in age, antral follicular count, AMH, protocol used or number of harvested oocytes were found between the groups. A higher gonadotropin starting dose in the pregnancy group (397.5±87 IU vs. 314.8±103 IU; P=0.02) and a trend to a higher total dose received (4720±1349 IU vs. 3871±1367 IU; P=0.07) were noted., Conclusions: The present study confirms that women with diminished ovarian reserve have low live birth rates after a first IVF-ICSI cycle and that a higher gonadotropin starting dose might be associated with better outcomes.

Background: Blood coagulation plays a crucial role in the blastocyst implantation process and its alteration may be related to in vitro fertilization (IVF) failure. We conducted a prospective observational longitudinal study in women eligible for IVF to explore the association between alterations of coagulation with the IVF outcome and to identify the biomarkers of hypercoagulability which are related with this outcome., Methods: Thirty-eight women eligible for IVF (IVF-group) and 30 healthy, age-matched women (control group) were included. In the IVF-group, blood was collected at baseline, 5-8 days after administration of gonadotropin-releasing hormone agonist (GnRH), before and two weeks after administration of human follicular stimulating hormone (FSH). Pregnancy was monitored by measurement of β HCG performed 15 days after embryo transfer. Thrombin generation (TG), minimal tissue factor-triggered whole blood thromboelastometry (ROTEM®), procoagulant phospholipid clotting time (Procoag-PPL®), thrombomodulin (TMa), tissue factor activity (TFa), factor VIII (FVIII), factor von Willebrand (FvW), D-Dimers and fibrinogen were assessed at each time point., Results: Positive IVF occurred in 15 women (40%). At baseline, the IVF-group showed significantly increased TG, TFa and TMa and significantly shorter Procoag-PPL versus the control group. After initiation of hormone treatment TG was significantly higher in the IVF-positive as compared to the IVF-negative group. At all studied points, the Procoag-PPL was significantly shorter and the levels of TFa were significantly higher in the IVF-negative group compared to the IVF-positive one. The D-Dimers were higher in the IVF negative as compared to IVF positive group. Multivariate analysis retained the Procoag-PPL and TG as predictors for the IVF outcome., Conclusions: Diagnosis of women with hypercoagulability and their stratification to risk of IVF failure using a model based on the Procoag-PPL and TG is a feasible strategy for the optimization of IVF efficiency that needs to be validated in prospective trials.

Deep infiltrating endometriosis (DIE) affects several anatomical locations including the bladder, torus uterinum, uterosacral ligament, rectovaginal septum and bowel. It is the most debilitating form of endometriosis and causes severe pain, digestive and urinary symptoms as well as infertility. Faced with an infertile woman suffering from DIE, the dilemma is whether to opt for first-line IVF treatment or for surgery. In the absence of high-level of evidence from randomized studies, several factors should be taken into account in the decision-making process. The main criterion is whether the patient wants in-vitro fertilization (IVF) treatment or not. Secondly, while previous reports have demonstrated the positive impact of surgery on pregnancy, they also underline the risk of severe complications requiring management in expert centers. Despite the availability of predictive models or scoring systems, the decision mainly boils down to the couple's characteristics. It seems logical to propose first-line IVF when spontaneous fertility is not possible due to associated male infertility or tubal obstruction; for women aged ≥35 years; or in women with diminished ovarian reserve. Conversely, first-line surgery could be the best option for women without these characteristics. However, this strategy is mainly based on low-level of evidence underlining the requiring of randomized trials.

Aim: Endometriosis affects from 10% to 15% of women of childbearing age and 20% of these women have deep infiltrating endometriosis (DIE). The goal of this review was to assess the impact of various locations of DIE on spontaneous fertility and the benefit of surgery and Medically Assisted Reproduction (MAR) (in vitro fertilization and intrauterine insemination) on fertility outcomes., Methods: MEDLINE search for articles on fertility in women with DIE published between 1990 and April 2013 using the following terms: "deep infiltrative endometriosis", "colorectal", "bowel", "rectovaginal", "uterosacral", "vaginal", "bladder" and "fertility" or "infertility". Twenty-nine articles reporting fertility outcomes in 2730 women with DIE were analysed., Results: Among the women with DIE and no bowel involvement (N.=1295), no preoperative data on spontaneous pregnancy rate (PR) were available. The postoperative spontaneous PR rate in these women was 50.5% (95% Confidence Interval [CI] =46.8-54.1) and overall PR (spontaneous pregnancies and after MAR) was 68.3% (95% CI=64.9-71.7). No evaluation of fertility outcome according to locations of DIE was feasible. For women with DIE with bowel involvement without surgical management (N.=115), PR after MAR was 29%; 95% CI=20.7-37.4). For those with bowel involvement who were surgically managed (N.=1320), postoperative spontaneous PR was 28.6% (95% CI=25-32.3) and overall postoperative PR was 46.9% (95% CI=42.9-50.9)., Conclusion: For women with DIE without bowel involvement, surgery alone offers a high spontaneous PR. For those with bowel involvement, the low spontaneous and relatively high overall PR suggests the potential benefit of combining surgery and MAR.

Background: To evaluate the impact of the association of endometrioma with or without deep infiltrating endometriosis (DIE) after a first intra cytoplasmic sperm injection- in vitro fertilization (ICSI-IVF) cycle on pregnancy rate., Materials and Methods: In this retrospective study, women with endometrioma who underwent a first ICSI-IVF cycle from January 2007 to June 2010 were reviewed for pregnancy rate. The main outcome measure was the clinical pregnancy rate. A multiple logistic regression (MLR) was performed; including all variables that were correlated to the conception rate. Only independent factors of pregnancy rate were included in a Recursive Partitioning (RP) model., Results: The study population consisted of 104 patients (37 without DIE and 67 patients with associated DIE). Using multivariable analysis, a lower pregnancy rate was associated with the presence of DIE (OR=0.24 (95% CI: 0.085-0.7); p=0.009) and the use of ICSI (OR=0.23 (95% CI: 0.07-0.8); p=0.02). A higher pregnancy rate was associated with an anti-mullerian hormone (AMH) serum level over 1 ng/ml (OR=4.3 (95% CI: 1.1-19); p=0.049). A RP was built to predict pregnancy rate with good calibration [ROC AUC (95% CI) of 0.70 (0.65-0.75)]., Conclusion: Our data support that DIE associated with endometrioma in infertile patients has a negative impact on pregnancy rate after first ICSI-IVF cycle. Furthermore, our predictive model gives couples better information about the likelihood of conceiving.