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The New England Journal of Medicine recently published a large study addressing the efficacy of preimplantation genetic testing for aneuploidy (PGT-A). The 14-centre randomized control non-inferiority trial used cumulative live birth rate (CLBR) as a clinical endpoint to examine the value of PGT-A and concluded that conventional IVF was not inferior to IVF with PGT-A. Unfortunately, the experimental design was highly flawed; and in fact, the data generated in the study do not support the major conclusions presented in the publication. The embryos in each patient's three-embryo pool, which were available for transfer, were selected solely by morphology. The investigators then randomized patients to either the PGT-A group or the control group. It is important to note that PGT-A screening in the study group was done only after the embryos were selected. PGT-A was not really used in a meaningful way, which would have been for the PGT-A results to help in selecting which embryos would be in the three-embryo group. Thus, the outcomes were wholly determined prior to the study intervention. The ultimate delivery rate for each group of three embryos was determined when they were selected by morphology. The randomization, which occurred after embryo selection, would assure equal distribution of those cohorts destined to deliver and those destined to fail to the two study groups, the PGT-A and control groups. Thus, there was no potential for PGT-A to enhance selection and thus no possible way to improve the cumulative outcomes. Since there was no possible way for the control group to be inferior, the experimental design precluded any chance of evaluating the primary endpoint of the study. The primary question of the study was never evaluated. Another serious flaw was that the study was initiated prior to knowing how to interpret the data provided in the PGT-A analytical result. Specifically, the design excluded mosaic embryos from transfer despite the literature demonstrating the significant reproductive potential for these embryos. When accounting for the lost deliveries induced by this non-evidence-based decision, the expected delivery rates in the two groups become virtually identical. That is an important issue because the data from the study actually demonstrate the safety of PGT-A without diminution in outcomes from the impact of trophectoderm biopsy or the discarding of competent embryos which had wrongfully been considered aneuploid. A final serious flaw in the experimental design and interpretation of the data surrounding the issue of the miscarriage rate. The investigators noted that the miscarriage rate was lower in the PGT-A group but stated that its impact was insufficient to alter the CLBR. Of course, by design, the CLBRs were limited to being equivalent. There was no potential for enhanced outcomes in the PGT-A group and thus no possibility that the lower risk of miscarriage in the PGT-A group would raise the CLBR. The benefit of a lower miscarriage rate is real and significant. Its relevance should not be diminished based on the lack of a change in the CLBR since that was never possible in this study. The investigators of the study concluded that the CLBR with conventional ART is equivalent to that with PGT-A, but a simple review of the experiment reassigns their genuine findings to those of a safety study. Significantly, the data in the study demonstrate that the intervention of PGT-A is safe. This study neither supports nor refutes the efficacy of clinical PGT-A., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To compare the ongoing pregnancy rates (OPRs) for subcutaneous progesterone (SC-P) to intramuscular progesterone (IM-P) in hormone replacement therapy used in frozen embryo transfer (FET) cycles., Design: Prospective nonrandomized cohort study., Setting: Private fertility clinic., Patients: The study enrolled 224 patients scheduled for hormone replacement therapy (HRT)-FET cycles with SC-P (n = 133) or IM-P (n = 91). The route of P administration was decided according to the patient's preference and accessibility to the hospital. In the first FET cycle of a freeze-all cycle using single blastocyst transfers, a woman aged ≤35 was included., Main Outcomes: Ongoing pregnancy (OP)., Results: The demographic, cycle, and embryologic characteristics were similar between groups. The clinical pregnancy rates (86/133[64.7%] vs. 57/91[62.6%]); miscarriage rates (21/86 [24.4%] vs. 10/57 [17.5%]), and OPR (65/133 [48.9%] vs. 47/91 [51.6%]) were comparable between the SC-P and IM-P groups. Binary logistic regression for OP as the dependent factor revealed that blastocyst morphology was found to be a significant independent prognosticator (for poor quality embryos adjusted odds ratio, 0.11; 95% confidence interval, 0.029-0.427) and progesterone route (SC-P vs. IM-P) was an insignificant prognosticator (adjusted odds ratio, 0.694; 95% confidence interval, 0.354-1.358)., Conclusions: The OPR for SC-P administration was similar to that for IM-P in HRT-FET cycles. The effect of ET-day P levels may vary regarding the administration route. Randomized controlled trials comparing different P administration routes are needed, and large-scale prospective trials are warranted to evaluate the ET-day P levels on pregnancy outcome., (© 2022 The Authors.)

Before the first live birth following uterus transplantation (UTx) in 2014, the 1-2% of women with an absent or non-functional uterus had no hope of childbearing. With 64 cases of UTx and 34 births reported in the scientific literature, this emerging technology has the potential for translation into mainstream clinical practice. However, limitations currently include donor availability, recipient suitability, surgical challenges regarding success and complications, and recipient management after UTx and during pregnancy. This review considers these challenges and ways to overcome them so that UTx could become part of the reproductive specialist's armamentarium when counselling patients with uterine factor infertility., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Due to various iatrogenic and social factors, the global caesarean delivery (CD) rate has risen sharply in the past 30 years. It is more complicated and dangerous for women with a scarred uterus to experience pregnancy again than for women with a previous vaginal delivery (VD). In this study we investigated the impact of previous caesarean delivery (CD) and caesarean scar defects (CSDs) on pregnancy outcomes after in vitro fertilization frozen-thawed embryo transfer (IVF-FET)., Methods: We conducted a retrospective cohort study that included 1122 women aged < 40 years who had a history of only one parturition (after 28 weeks of pregnancy) and who underwent their first FET cycle between January 2014 and January 2020. Patients were divided into the CD group, VD group, and CSD group. Thereafter, according to the number of transferred embryos, the CD, VD, and CSD groups were divided into the single embryo transfer (SET) group and the double embryo transfer (DET) group. Outcome measures in this study were live birth, clinical pregnancy, multiple pregnancy, ectopic pregnancy, pregnancy loss, pregnancy complications, preterm birth, and neonatal birth weight. Multivariate logistic regression was performed to evaluate the relationship between pregnancy outcomes and CD., Results: In SET patients, the clinical pregnancy and live birth rates were decreased in the CSD group compared with the VD and CD groups. In DET patients, the clinical pregnancy and live birth rates were significantly lower in theCSD group than in the CD and VD groups. After adjustment for confounders, previous CD and CSD were associated with a significantly lower clinical pregnancy rate and live birth rate than previous VD in the total sample. This effect was observed in DET patients, but not in SET patients. Additionally, DET patients with previous CD had a significantly higher multiple pregnancy rate (AOR = 0.47, 95% CI = 0.29, 0.75, P = 0.002) than those with previous VD, but no significant associations were observed in CSD and multiple pregnancies (AOR = 0.55, 95% CI = 0.23, 1.34, P = 0.192) between DET patients with CD and those with VD after adjusting for potential confounders., Conclusions: Our study showed that during an FET cycle, previous CD and the presence of a CSD could negatively affect pregnancy outcomes especially in DET patients., (© 2022. The Author(s).)

This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success.

Objective: To study the consequences of specific genotype profiles of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone choriogonadotropin receptor (LHCGR) on assisted reproductive technology outcomes when preimplantation genetic testing for aneuploidy is used for controlling the embryo ploidy status. The most common reported single-nucleotide polymorphisms in the amino acid position for the FSHR (N680S; N: asparagine, S: serine; [rs6166]) and the LHCGR (N312S variant; N: asparagine, S: serine [rs2293275]) were chosen for this study., Design: Retrospective cohort study., Setting: Private Fertility Clinic., Patient(s): All women aged 18-40 years undergoing their first assisted reproductive technology cycle with aneuploidy screening between 2006 and 2017 with body mass index of >18 and <40 kg/m 2 were included., Intervention(s): All patients received both recombinant follicle-stimulating hormone and human menopausal gonadotropin or low dose human chorionic gonadotropin. Genomic DNA was isolated from patients' blood. Genotyping of the FSHR and LHCGR polymorphisms was performed using TaqMan genotyping assays. Associations between both receptor genotypes and clinical outcomes were assessed using generalized regression and ANOVA., Main Outcomes Measure(s): Live birth rate was the primary outcome. Secondary outcomes included oocyte yield, mature oocytes, blastulation rate, usable blastocyst rate, and implantation rate., Result(s): A total of 1,183 patients met the inclusion criteria and generated reliable genotype results. The overall genotype frequencies in the study population for the FSHR gene were as follows: 21.7% homozygous for S in codon 680, 29.2% homozygous for N680, and 48.1% heterozygous (N680S). As for the LHCGR, 15.6% were homozygous for N312, 38.5% homozygous for S312 and 45.9% heterozygous (N312S). Our study population consisted of 53.8% non-Hispanic white; 6.1% Hispanic white; 4.1% Afro-American; 15.4% Asian; and 20.6% other or unknown. No significant association was found with any of the studied variables (oocyte yield, usable blastocyst rate, implantation rate, live birth) when genotypes were analyzed per receptor or in combination with one another. There was a statistically significant but clinically irrelevant difference in the rate of mature oocytes across different variant combinations., Conclusion(s): Our findings suggest that the presence of gonadotropin receptor polymorphisms in both FSHR N680S and LHCGR N312S are not associated with assisted reproductive technology outcomes; therefore, these variants should not be considered reproductive predictors., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Endometriosis was classically diagnosed during diagnostic laparoscopies, which used to be routinely performed up until a decade ago or so. This practice fitted with the long-held belief that surgery was the gold standard for diagnosing endometriosis. Today, the abandon of routine diagnostic laparoscopies-in favor of assisted reproductive technology-first therapeutic approaches-has created a void for diagnosing endometriosis. Modern-day imaging techniques-ultrasound and magnetic resonance imaging-when used with a systematic approach have offered a reliable replacement option for diagnosing endometriosis. In infertility, endometriosis should be identified or excluded on the basis of past history or confirmation or exclusion suspicion on the basis of history and/or physical examination., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The workup of patients seeking assisted reproductive technology (ART) treatments has been modified by the tremendous improvements in ART efficacy accomplished recently. Moreover, the fact that ART is nowadays also offered to women who are not necessarily infertile-seeking genetic testing of their embryos-lead to important changes in how we investigate ART candidates. All the facets of these changes have been reviewed in the present introduction to this View-and-Review series on modern-day infertility workups., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Ovarian response indexes have been proposed in assisted reproductive technology (ART) in order to optimize live birth rates (LBR), adjusting ovarian stimulation (OS), and minimizing risks. Gonadotropin doses are commonly adjusted according to ovarian reserve parameters, including antral follicle count (AFC), anti-Mullerian hormone (AMH), and basal follicle stimulating hormone (FSH) levels. The retrospective assessment of ovarian responses allows one to identify three primary indexes: (i) follicular output rate (FORT), the ratio of the number of pre-ovulatory follicles obtained at OS completion over AFC; (ii) follicle oocyte index (FOI), the ratio of oocytes retrieved over AFC; (iii) ovarian sensitivity index (OSI), the ratio of oocytes retrieved over the total gonadotropin dose administered. In recent publications, these indexes were reported to predict ART outcome. In the present study, we assessed the ability of these indexes to predict cumulative ART outcome in women ≥39 years. Materials and Methods: Retrospective cohort study. All patients ≥39 years who performed their first ART cycle with an antagonist protocol in our center between 01/2018 and 04/2020 were included. Patients with basal FSH > 20 IU/l, AMH < 0.1 ng/mL and severe male factors (azoospermia with testicular biopsy) were excluded. All patients received both recombinant FSH and human menopausal gonadotropin (hMG). Cumulative live birth rate (cLBR) was the primary outcome. Secondary outcomes included: the number of MII oocytes, cumulative implantation (cIR), and usable blastulation rates. Logistic regressions were performed to assess the predictive values of FORT, FOI, and OSI in cLBR and embryo culture success. For each parameter, the ability of the logistic regression models to predict embryo culture success was quantified by the area under the ROC curve (AUC). Only the significant findings related to FORT, FOI, and OSI were included in the multiple logistic regression model. Linear regression models were performed between cIR, cLB, FORT, FOI, and OSI. Each statistic model was adjusted for age. Concerning OR for OSI, values were multiplied *100 due to the very low value. Results: 429 patients met the inclusion criteria. There were 298 obtained usable blastocysts after ART treatment. Age-adjusted OSI was significantly associated with cLBR [OR = 17.58 95% CI (5.48−56.40), AUC = 0.707 95% CI (0.651−0.758)) and cIR (beta = 30.22 (SE: 7.88), p < 0.001, R2= 0.060). Both FOI (OR = 6.33 95% CI (3.27−12.25), AUC = 0.725 95% CI (0.675−0.771), R2 = 0.090, p < 0.001) and OSI (OSI*100; OR = 1808.93 95% CI (159.24−19,335.13), AUC = 0.790 95% CI (0.747−0.833), R2 = 0.156, p < 0.001) were independently, when age adjusted, associated with embryo culture success. OSI showed a main performance to explain successful embryo culture than FOI (R2 = 0.156 vs. R2 = 0.090, p < 0.001). In the age-adjusted linear regression model, FOI (R2 = 0.159, p < 0.001), OSI (R2 = 0.606, p < 0.001), and FORT (r2 = 0.030, p < 0.001) were predictive of the number of MII oocytes collected. Furthermore, for OSI (r2 = 0.759, p < 0.001) and FOI (r2 = 0.297, p < 0.001), the correlation with the number of metaphase II oocytes collected was significantly higher in the non-linear regression model. Conclusions: Our findings suggest that the best index, among those analyzed, to predict cIR and cLBR, is OSI. Both OSI and FOI predict embryo culture with success, but OSI is more accurate. OSI, FOI, and FORT are significantly related to the number of MII oocytes obtained.

Background: Absolute uterine factor infertility affects 0. 2% women of childbearing age around the world. Uterine transplantation (UTx) is a promising solution for many of them since the first birth from UTx was described by the Swedish team in 2014. The success of Utx in humans has become possible after a systematic and meticulous approach involving years of research on animal models. To date, more than 80 UTx procedures have been performed worldwide and 30 children were born., Material and Method: This review summarizes the research preparation conducted in animals before beginning UTx in humans. It focuses on the advantages and limits of each animal model, their place in surgical training, and current contribution in research to improve UTx successes in humans. The different steps in the process of UTx have been analyzed, such as imaging, surgery, ischemia-reperfusion effects, rejection markers, immunosuppressive treatment, and pregnancy., Conclusion: Animal models have played an essential role in the implementation of UTx, which is a highly complex procedure. While respecting the 3R requirements (replacement, refinement, and reduction), the surgical training using large animal models, such as notably ewes remain irreplaceable for teams wishing to initiate a UTx program. Furthermore, animal models are still mandatory in current research to improve the success rates of UTx in humans as well as to reduce the morbidity associated with this experimental infertility treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Favre-Inhofer, Carbonnel, Domert, Cornet, Chastant, Coscas, Vialard, Gelin, Galio, Richard, Trabelsi, Sandra, de Ziegler, Chavatte-Palmer and Ayoubi.)

Purpose: The current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138., Methods: This is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC., Results: Sensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761-0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138., Conclusion: IHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recurrent implantation failure (RIF) is an undefined, quite often, clinical phenomenon that can result from the repeated failure of embryo transfers to obtain a viable pregnancy. Careful clinical evaluation prior to assisted reproduction can uncover various treatable causes, including endocrine dysfunction, fibroid(s), polyp(s), adhesions, uterine malformations. Despite the fact that it is often encountered and has a critical role in Assisted Reproductive Technique (ART) and human reproduction, RIF's do not yet have an agreed-on definition, and its etiologic factors have not been entirely determined. ART is a complex treatment with a variable percentage of success among patients and care providers. ART depends on several factors that are not always known and probably not always the same. When confronted with repeated ART failure, medical care providers should try to determine whether the cause is an embryo or endometrium related. One of the most common causes of pregnancy failure is aneuploidy. Therefore, it is likely that this represents a common cause of RIF. Other RIF potential causes include immune and endometrial factors; however, with a very poorly defined role. Recent data indicate that the possible endometrial causes of RIF are very rare, thereby throwing into doubt all endometrial receptivity assays. All recent reports indicate that the true origin of RIF is probably due to the "egg".

The recent advent of embryo vitrification and its remarkable efficacy has focused interest on the quality of hormone administration for priming frozen embryo transfers (FETs). Products available for progesterone administration have only been tested in fresh assisted reproduction technologies (ARTs) and not in FET. Recently, there have been numerous concordant reports pointing at the inefficacy of vaginal preparations at delivering sufficient progesterone levels in a sizable fraction of FET patients. The options available for coping with these shortcomings of vaginal progesterone include (i) rescue options with the addition of injectable subcutaneous (SC) progesterone at the dose of 25 mg/day administered either solely to women whose circulating progesterone is <10 ng/mL or to all in a combo option and (ii) the exclusive administration of SC progesterone at the dose of 25 mg BID. The wider use of segmented ART accompanied with FET forces hormone replacement regimens used for priming endometrial receptivity to be adjusted in order to optimize ART outcomes.

Gender dysphoria, a discrepancy between gender identity and genetically determined sex, is encountered in approximately 0.5% of people uniformly across the world. In the case of transgender men, formerly called female-to-male transsexuals, the available gender-affirming measures, hormone therapy and possible surgical procedures, are multiple and discussed in detail in this series of articles., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

To assess the relation between oocytes yield including total retrieved oocytes (O)c and total mature oocytes (MII) relative to the antral follicular count (AFC) (3-9 mm in diameter) and relative to anti-müllerian hormone (AMH) ng/mL level: Oc/AFC, MII/AFC, Oc/AMH, and MII/AMH, respectively, and ART outcomes. We included retrospectively 264 IVF cycles after the first embryo transfer (ET) and after the cumulative ET (CET). The implantation rate (IR) and the live birth rate (LBR) after first ET were 31 ± 39% and 32.6%, respectively, and after CET 35 ± 38% and 45.1%, respectively. There was a significantly higher average of Oc/AFC and MII/AFC when live birth (LB) occurred after the first ET (0.82 ± 0.4 vs. 0.71 ± 0.35 and 0.57 ± 0.4 vs. 0.68 ± 0.3, respectively, P < 0.05). We reported a significantly higher average of MII/AFC when LB occurred after CET (0.66 ± 0.3 vs. 0.56 ± 0.30, P = 0.02) in comparison to the group where no LB was obtained. Increased Oc/AFC and MII/AFC ratios were associated with the occurrence of LB and increased IR after first ET ( P < 0.05). Increased MII/AFC ratio was associated with the occurrence of LB and IR after CET ( P = 0.02 and P = 0.04, respectively). After age-adjusted multivariate analyses, all these trends were confirmed ( P < 0.05) except for the effect of MII/AFC ratio on IR after CET. In conclusion, Oc/AMH and MII/AMH ratios have no effect on the occurrence of LBR or on IR after first ET or CET at either age grouping. Ratios Oc/AFC and MII/AFC seem promising indicators to assess ovarian response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Poulain, Younes, Pirtea, Trichereau, Ziegler, Benammar and Ayoubi.)

Purpose of Review: To clarify a lingering issue, the true incidence of repeated implantation failures (RIF) in women undergoing successive frozen euploid single embryo transfers (FE-SET)., Recent Findings: As not all Assisted reproductive techinique (ART) attempts are crowned by success, it has been questioned since incept of ART whether failures resulted from an embryonic or endometrial cause. RIF has received no precise definition but a trend has existed toward setting a more stringent definition, as reproductive biology has become more effective and ART success rates improved. No scientific society has yet convened on a universally accepted definition. The advent of effective and well tolerated pregestational testing of embryos for aneuploidy (PGT-A) has allowed to not transfer aneuploid embryos, which are bound not to succeed. This, therefore, justify revisiting the concept of RIF when only euploid embryos are transferred., Summary: Contrary to lingering beliefs, the results of our study indicate that RIF following three successive euploid embryo transfers in a morphologically normal endometrium is a rare occurrence (<5%). This supports the concept that ART failures mainly result from embryonic causes. Our data also propose a new - functional - definition of RIF being an ART failure following 3 successive FE-SET attempts. Our findings, therefore seriously question the soundness of prescribing the often complex and expensive endometrial testing procedures that largely publicized for treating RIF., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

To evaluate the expression of genes encoding cytokines, grow factors and cell cycle regulators in the proliferative endometrium of women with chronic endometritis (CE) compared to controls. We performed a case-control study on seven women with CE as diagnosed by hysteroscopy and histology (Cases) compared to six women without CE (Controls). All women underwent diagnostic hysteroscopy plus endometrial biopsy during the mid-proliferative phase of the menstrual cycle. Endometrial samples were divided into two different aliquots for histological and molecular analyses. The endometrial expression profile of 16 genes encoding proteins involved in the inflammatory process, proliferation and cell cycle regulation/apoptosis was assessed by using high-throughput qPCR. Study endpoints were between-group differences in the expression of VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1, BAX and IL12. RESULTS: VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1 were significantly overexpressed in women with CE compared to controls, while BAX and IL12 had similar expression between groups. In women with CE, we found an altered endometrial expression of genes involved in inflammatory, cell proliferation, and apoptosis processes. The dominance of proliferative and anti-apoptotic activity in CE may potentially promote the development of polyps and hyperplastic lesions.

Congenital and acquired uterine anomalies are associated with recurrent pregnancy loss (RPL). Relevant congenital Müllerian tract anomalies include unicornuate, bicornuate septate, and arcuate uterus. Recurrent pregnancy loss has also been associated with acquired uterine abnormalities that distort the uterine cavity such as, notably, intrauterine adhesions, polyps, and submucosal myomas. Initial evaluation of women with RPLs should include an assessment of the uterine anatomy. Even if proof of efficacy of surgical management of certain uterine anomalies is often lacking for managing RPLs, surgery should be encouraged in certain circumstances for improving subsequent pregnancy outcome. Uterine anomalies such as uterine septa, endometrial polyps, intrauterine adhesions, and submucosal myomas are the primary surgical indications for managing RPLs., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Recurrent pregnancy loss (RPL), defined as two to three spontaneous pregnancy terminations occurring before 12 weeks of gestation, affects approximately 1% of the general population. The causes may include congenital factors that originate with the quality of the gametes (sperm or oocyte) or the resulting embryo, or factors that originate within the uterus. Alterations of endometrial receptivity from endometriosis and/or endometritis, which are associated with impaired action of progesterone, have also been implicated in RPL. Finally, immunologic factors and thrombophilia, congenital and acquired, have also been suspected to cause RPL., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Chronic inflammatory processes affecting the endometrium, as encountered in endometriosis, adenomyosis, and chronic endometritis, alter endometrial receptivity. These disorders are associated with early pregnancy losses and possibly recurrent pregnancy losses (RPL). In the cases of endometriosis, other factors associated with the disease also are susceptible of causing miscarriages and possibly RPL, such as an impact of intrapelvic inflammatory processes affecting the oocyte and embryo in case of natural conception. Conversely these latter effects obviously are bypassed in case of assisted reproductive technology. Chronic inflammation of the endometrium in the condition known as chronic endometritis also causes early pregnancy losses and RPL with beneficial effects achieved when specific treatment is undertaken., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the true prevalence of recurrent implantation failure., Design: Retrospective cohort study., Setting: A private assisted reproductive technology center., Patient(s): Women (n = 4,429) with anatomically normal uterus who underwent up to three consecutive frozen euploid single embryo transfers (FE-SETs) were included in the study. Cycles with donor eggs or gestational carriers were excluded., Intervention(s): None., Main Outcome Measure(s): Cumulative outcomes from these cycles were analyzed. A logistic regression model was used to assess the differences of outcomes between first, second, and third FE-SET and a Kaplan-Meier curve as used to analyze cumulative implantation rate., Result(s): The mean age of the patients included in the study was of 35.4 years. The sustained implantation rates of the first, second, and third FE-SET were 69.9%, 59.8%, and 60.3% per transfer, respectively. The cumulative sustained implantation rate after up to three consecutive FE-SET was 95.2%. The live birth rates after the first, second, and third FE-SET were 64.8%, 54.4%, and 54.1% per transfer, respectively. The cumulative live birth rate after up to three consecutive FE-SET was 92.6%. The miscarriage rate after observing a positive heartbeat was not different between the first (7.2%), second (8.8%), and third (12.7%) FE-SET., Conclusion(s): Our findings suggest that true recurrent implantation failure is rare. For those patients with the ability to make euploid blastocysts, <5% would fail to achieve a clinical pregnancy with three embryos transferred. It remains to be further investigated whether this threshold identifies a truly recalcitrant group or simply a statistical certainty based on random variation., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Obstetrics and Gynecology department in France were not ready for the outbreak of the COVID pandemic, but ingenuity and dedication of personnel allowed to perform safely and avoid nocomial transmission of COVID.

Assisted reproductive technology (ART) has been so widely deployed across the world that over 1% of all births are now ART babies, with even higher percentages in the Nordic countries. As pregnancy rates are limited by technical, population, and inherent limitations of human reproduction, key performance indicators should be defined for all the different facets of ART to measure the efficacy of the procedure., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Like all industries, fertility clinics should identify and follow reference markers of its activity-key performance indicators (KPI)-to allow assisted reproductive technology outcomes to be monitored and compared. Clinical KPIs revolve around following set parameters of the patient population, procedures, and outcome data. Moreover, KPIs should also include identified protocols and standard operating procedures followed in daily practice and should keep track of multiple pregnancy rates, a ruthless confounder of assisted reproductive technology outcomes., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

We report our experience regarding the profile and screening process of potential recipients (R) and their live donors (D) in our Uterus transplantation (UTx) trial from 2014 to 2020. The initial screening was performed using medical questionnaires and consultations. The second step of the screening consisted of two individual interviews with an independent multidisciplinary committee. Then, a complete medical, biological and imaging assessment of the directed living D, the R, and her partner was performed over a two-day hospitalization. A total of 239 women contacted our department: 165 potentials R and 74 potentials D. During the first step of screening, 141 R and 45 D were excluded. Only 12 R/D pairs were pursued. During inclusion, 10 R/D pairs were excluded. One R/D pair is still under evaluation. Finally, only 1 R/D pair was definitively included (0.6%), which led us to perform the first French UTx in March 2019 with a successful graft. The primary limiting factors of inclusion were due to very strict criteria and difficulty of having a suitable directed living D. The International Society of UTx (ISUTx) guidelines based on worldwide results of trials can help ease our inclusion criteria in the future while remaining safe for patients.

Study Objective: To investigate the correlation between endometrial polyps (EPs) and chronic endometritis (CE)., Design: Single-center retrospective case-control study., Setting: Academic center., Patients: A total of 480 premenopausal women with abnormal uterine bleeding (AUB) were enrolled. Group A included 240 women suffering from EPs (diagnosed by hysteroscopy and histology), and group B included 240 patients without EPs at hysteroscopy., Interventions: In group A, 2 separate samples were obtained from the EPs (group A polyps) and endometrium (group A endometrium). In group B, a single sample of endometrial tissue was evaluated (group B endometrium). All tissue samples were subjected to immunohistochemistry for CD-138 for plasma cell identification., Measurements and Main Results: The primary study endpoint was to compare the rates of CE in group A endometrium versus group B endometrium. The secondary endpoint was to evaluate the consistency in CD-138 immunoreactivity between group A polyps and compared with group A endometrium. A higher prevalence of CE was observed in group A endometrium compared with group B endometrium (p < .0001). The total percentage of EPs showing CD-138 positivity was 76.7% (184 of 240). CE was more frequent in women with CD-138 + EPs compared to those with CD-138 - EPs (p < .0001)., Conclusions: EPs were commonly associated with CE in the premenopausal women suffering from AUB. Moreover, the majority of EPs were positive for CD-138 staining, suggesting a possible hidden association between chronic inflammation and EPs., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Ovarian stimulation (OS) has for objective to induce multiple ovulation in order to yield a multiple oocyte harvest and offer multiple embryos available for transfer thereby increasing the efficacy of ART. Originally, the primary risk associated with OS was the occurrence of frank ovarian hyperstimulation syndrome (OHSS), a possibly dreadful-sometime fatal-complication of ART. These fears limited the number of oocytes aimed for during OS in order to curb the risk of OHSS. On the contrary, the meager implantation rates of the early days of ART led to easily transfer multiple embryos in order to achieve acceptable pregnancy rates. Today the perspectives have changed. The advent of antagonist-based OS protocol and the possibility to trigger the ultimate phase of oocyte maturation with GnRH-a has allowed to reduce the risk of OHHS. Conversely, the markedly increased implantation rates of today's ART makes multiple pregnancy a worry that has come in the limelight worldwide, pushing the practice of single embryo transfer (SET).

Introduction: Intra-uterine adhesion (IUA) is one of the main causes of secondary infertility. The aim of this study was to evaluate the prevalence of IUA developing in women undergoing hysteroscopic resection for submucous myomas, polyps, and intrauterine synechiae and test the efficacy of second look hysteroscopy for diagnosing and treating post-surgical adhesions. Materials and Methods: We retrospectively collected data from reproductive age women who had a second look office hysteroscopy following hysteroscopic resection for myoma, polyp, or IUA at Foch hospital (Suresnes, France) between 2009 and 2017. Results: Six hundred and twenty two reproductive-age women underwent hysteroscopic resection for myoma, polyp, and/or IUA. Among them, 155 women had a second look hysteroscopy. In this group, 29/155 (18.7%) had IUA formation: 17/83 (20.5%) women who underwent hysteroscopic myomectomy, 5/46 (10.9%) women who underwent hysteroscopic polypectomy, and 7/26 (26.9%) women who underwent hysteroscopic lysis of adhesions. These IUA have been lysed by the office hysteroscopy procedure in 16/29 (55.2%) patients: 11/17 (64.7%), 2/5 (40%), and 3/7 (42.9%) in women who underwent hysteroscopic myomectomy, polypectomy and lysis of adhesion, respectively. Conclusion: IUA is a common complication of hysteroscopic surgery. Second look office hysteroscopy is an easy and effective procedure for diagnosing and removing newly formed IUA. It should be recommended for all women undergoing hysteroscopic resection for myomas, polyps, or IUA.

The development of assisted reproductive technology (ART) through four decades has led to offer the ultimate treatment for nearly all forms of infertility. The only remaining factor of childlessness however that still eludes ART and its routine variants are the absolute uterine infertility factors, for which the only option is an experimental approach, uterus transplantation. Progresses has been made over the past few years, and more are underway for simplifying the process notably for simplifying the uterus extraction step performed in the uterus donor. Furthermore, as the technique is being better mastered, the original indications for uterus transplantation, the congenital or acquired absence of the uterus, are now widened to also include incurable uterine fibrosis, or Asherman's syndrome. The ART-related practicalities of uterus transplantation, ovarian stimulation and uterine priming are being discussed in the present review., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Endometriosis - a disease causing pain and infertility - is encountered in nearly 50% of infertile women. While medical treatment is effective on pain and recurrence of symptoms after surgical excision, it is of no help for treating infertility for which the only options considered are surgery and ART. Surgery enhances the chances of conceiving naturally during the 12-18 ensuing months irrespective of the stage of the disease. Surgery however is of no help when ART is considered, as it does not improve outcome and can only harm the ovarian response to stimulation. Today therefore, ART is commonly the primary option to be considered in women whose infertility is associated with endometriosis and whose ovarian reserve is compromised and/or who are over 35 years of age. When, ART is envisioned it is best to opt for a segmented ART approach with agonist trigger, freeze all and deferred embryo transfer., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To study the prevalence of oligo-anovulation in women suffering from endometriosis compared to that of women without endometriosis., Design: A single-center, cross-sectional study., Setting: University hospital-based research center., Patient (s): We included 354 women with histologically proven endometriosis and 474 women in whom endometriosis was surgically ruled out between 2004 and 2016., Intervention: None., Main Outcome Measure(s): Frequency of oligo-anovulation in women with endometriosis as compared to that prevailing in the disease-free reference group., Results: There was no difference in the rate of oligo-anovulation between women with endometriosis (15.0%) and the reference group (11.2%). Regarding the endometriosis phenotype, oligo-anovulation was reported in 12 (18.2%) superficial peritoneal endometriosis, 12 (10.6%) ovarian endometrioma, and 29 (16.6%) deep infiltrating endometriosis., Conclusion(s): Endometriosis should not be discounted in women presenting with oligo-anovulation., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Chronic endometritis is a persistent inflammation of the endometrial mucosa caused by bacterial pathogens such as Enterobacteriaceae, Enterococcus, Streptococcus, Staphylococcus, Mycoplasma, and Ureaplasma. Although chronic endometritis can be asymptomatic, it is found in up to 40% of infertile patients and is responsible for repeated implantation failure and recurrent miscarriage. Diagnosis of chronic endometritis is based on hysteroscopy of the uterine cavity, endometrial biopsy with plasma cells being identified histologically, while specific treatment is determined based on microbial culture. However, not all microorganisms implicated are easily or readily culturable needing a turnaround time of up to 1 week., Objective: We sought to develop a molecular diagnostic tool for chronic endometritis based on real-time polymerase chain reaction equivalent to using the 3 classic methods together, overcoming the bias of using any of them alone., Study Design: Endometrial samples from patients assessed for chronic endometritis (n = 113) using at least 1 or several conventional diagnostic methods namely histology, hysteroscopy, and/or microbial culture, were blindly evaluated by real-time polymerase chain reaction for the presence of 9 chronic endometritis pathogens: Chlamydia trachomatis, Enterococcus, Escherichia coli, Gardnerella vaginalis, Klebsiella pneumoniae, Mycoplasma hominis, Neisseria gonorrhoeae, Staphylococcus, and Streptococcus. The sensitivity and specificity of the molecular analysis vs the classic diagnostic techniques were compared in the 65 patients assessed by all 3 recognized classic methods., Results: The molecular method showed concordant results with histological diagnosis in 30 samples (14 double positive and 16 double negative) with a matching accuracy of 46.15%. Concordance of molecular and hysteroscopic diagnosis was observed in 38 samples (37 double positive and 1 double negative), with an accuracy of 58.46%. When the molecular method was compared to microbial culture, concordance was present in 37 samples (22 double positive and 15 double negative), a matching rate of 56.92%. When cases of potential contamination and/or noncultivable bacteria were considered, the accuracy increased to 66.15%. Of these 65 patients, only 27 patients had consistent histological + hysteroscopic diagnosis, revealing 58.64% of nonconcordant results. Only 13 of 65 patients (20%) had consistent histology + hysteroscopy + microbial culture results. In these cases, the molecular microbiology matched in 10 cases showing a diagnostic accuracy of 76.92%. Interestingly, the molecular microbiology confirmed over half of the isolated pathogens and provided additional detection of nonculturable microorganisms. These results were confirmed by the microbiome assessed by next-generation sequencing. In the endometrial samples with concordant histology + hysteroscopy + microbial culture results, the molecular microbiology diagnosis demonstrates 75% sensitivity, 100% specificity, 100% positive and 25% negative predictive values, and 0% false-positive and 25% false-negative rates., Conclusion: The molecular microbiology method describe herein is a fast and inexpensive diagnostic tool that allows for the identification of culturable and nonculturable endometrial pathogens associated with chronic endometritis. The results obtained were similar to all 3 classic diagnostic methods together with a degree of concordance of 76.92% providing an opportunity to improve the clinical management of infertile patients with a risk of experiencing this ghost endometrial pathology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Luteal phase support is mandatory in ovarian stimulation cycles in assisted reproductive technology owing to a deficit in LH pulsatility after the effects of exogenous hCG-used for triggering ovulation-vanish. This is classically accomplished by means of exogenous P administration, but emerging new options include microdoses of hCG and exogenous GnRH agonist. Although luteal phase support is commonly continued for up to 10 weeks into pregnancy, there is accumulating evidence that it can be stopped after the first ultrasound or even after a positive pregnancy test., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Progesterone elevation occurring in the late phases of controlled ovarian stimulation (COS) has been reported for over 25 years. Yet doubts remain regarding the mechanisms at play in this phenomenon and its net consequences on assisted reproductive technology outcome, which is known to occur in poor and good assisted reproductive technology responders. The pathophysiology of end-COS progesterone elevation encountered in gonadotropin-suppressed cycles is different from that prevailing at the time of, and just after, ovulation. The different divergence in practical consequences of end-COS progesterone elevation led to review the progesterone assays developed for measuring progesterone in the luteal phase of the menstrual cycle, but commonly used for measuring all forms of progesterone elevation., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Over the past decades many of us have contributed to the controversy surrounding the origins and consequences of premature progesterone elevation during controlled ovarian stimulation. In this article, we attempt to retrace the progression of information on this complex subject which required reviewing a number of publications that often contradicted one another. The definition of premature progesterone elevation, the pathophysiological mechanisms underlying the high peripheral progesterone levels, and the debated consequences of this event on in vitro fertilixation-embryo transfer outcome will be addressed from a historical perspective., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)