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The countercurrent opinion given in this paper is that the optimal management of frozen embryo transfers (FET) is not a one-size-fits-all matter, but rather one that should be decided after considering all the various parameters and options. This choice should notably encompass patients' individual characteristics - including variable risks of obstetric complications - and weigh out the respective advantages of each FET option in each case. While there may be real advantages for natural-cycle FET in many cases, these need to be balanced against both practical and clinical issues. Contrary to several prevailing, sometimes loudly expressed suggestions, there is not a one single effective approach when it comes to choosing a mode of scheduling FET., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study is to review patient experience with social fertility preservation (sFP), as compared to medical fertility preservation (mFP), in a context where sFP is fully reimbursed., Methods: We conducted a retrospective cohort study involving patients who underwent oocyte cryopreservation for mFP between 2017 and 2023 and sFP between 2022 and 2023 at a large ART single center. Additionally, we surveyed patients undergoing sFP and mFP, regarding their experiences, intentions, awareness, and financial consideration., Results: A total of 97 oocyte retrievals were performed for sFP in 75 women, and 155 were performed in mFP (127 women). Median ages were 36.4 years for sFP and 28.9 years for mFP. Median oocytes retrieved per session were 10 for sFP and 8 for mFP. Ninety-seven percent of of mFP participants were informed by healthcare professionals, while half of sFP participants learned through personal acquaintances. The primary motivation for sFP was a desire for pregnancy while being single. Most respondents in both groups knew that 15-20 oocytes are typically needed for a successful birth. None were aware of the "DuoStim" option, but interest was expressed by most women. Surprisingly, despite full reimbursement for sFP in France, 78% expressed willingness to pay if necessary., Conclusion: Many women choose sFP due to concerns about declining fertility, often informed by non-medical sources. Free access to sFP can help mitigate the global decline in natality by allowing women to anticipate age-related fertility decline. This study should be considered by other countries as they may increasingly cover sFP costs in the future., (© 2024. The Author(s).)

Ovarian stimulation (OS) has been the single most effective measure ever taken for enhancing assisted reproductive technology outcomes. In the past decade, we have seen a flurry of various new protocols used for OS in assisted reproductive technology In light of the important differences that characterize these new approaches for OS, we felt it was timely to review the relative merits of each and every new protocol., Competing Interests: Declaration of Interests D.d.Z. has nothing to disclose. S.S. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Adenomyosis is an important clinical condition with uncertain prevalence, and clinical focus on adenomyosis in patients undergoing assisted reproductive technology (ART) has increased during recent years. Recognizing the limited clinical knowledge on the impact of adenomyosis on ART outcomes, the First Lugano Adenomyosis Workshop was a symposium involving experts in the field of adenomyosis, covering basic research, imaging, surgery and infertility to highlight current advances and future research areas over a wide range of topics related to adenomyosis. Adenomyosis is characterized by altered oestrogen and progesterone signalling pathways. Although the criteria of the Morphological Uterus Sonographic Assessment (MUSA) Consortium apply to patients with infertility, the presence of direct signs and localization in the different myometrial layers, particularly the inner myometrium, need more focus. In addition to the MUSA criteria, clinical symptoms and the magnitude of uterine enlargement should also be considered. Whilst pre-treatment with gonadotrophin-releasing hormone agonist with or without an aromatase inhibitor in frozen embryo transfer cycles seems promising, many issues related to therapy remain unanswered. During the Workshop, therapeutic progress over the past decades as well as novel insights were presented and discussed. The role of this opinion paper is to stimulate discussion and spark further interest in adenomyosis and the role of adenomyosis in infertility., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Ovarian stimulation has been the single most efficient measure ever taken in assisted reproductive technology for improving outcomes by harvesting multiple oocytes and ultimately, embryos. Today, ovarian stimulation protocols consist of administrating exogenous gonadotropins to override the natural mechanisms that control the ovulatory quota to one in humans. For practicality issues, there have been numerous attempts to control, or "program," when ovarian stimulation is initiated to improve functionality and in turn efficacy for assisted reproductive technology programs. The different options for controlling the onset of ovarian stimulation currently available are discussed here, as well as the novel possibility of using progestins for blocking premature ovulation., Competing Interests: Declaration of Interests S.S. has nothing to disclose. P.O. has nothing to disclose. C.T. has nothing to disclose. D.d.Z. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to review recent data that affected the clinical management of infertility associated with endometriosis., Data Sources: We completed a PubMed review of all articles that included the following keywords: endometriosis, infertility, IVF, and ART., Study Selection: A study was selected based on the pertinence of the topic addressed in relation to the study's set objectives., Data Extraction and Synthesis: All identified articles were first assessed based on a review of the abstract. Pertinent articles were reviewed in depth., Conclusion: Endometriosis interferes with natural conception primarily by altering the quality of gametes-oocytes and sperm-and early-stage embryos. On the contrary, recent data indicate that gametes and early-stage embryos are not altered in the case of ART. Surgery-a classical approach in yesteryears-does appear to improve ART outcomes and may affect ovarian reserve and the number of oocytes retrieved in ART. Surgery is thus more rarely opted for today and only when necessary; proceeding to fertility preservation prior to surgery is recommended. When ART is performed in women with endometriosis, it is recommended to use an antagonist or progesterone-primed ovarian stimulation approach followed by deferred embryo transfer. In this case, GnRH (gonadotropin releasing hormone) agonist is preferred for triggering ovulation, as it limits the risk of cyst formation as well as ovarian hyperstimulation syndrome. Frozen embryo transfers are best performed in E2 (estradiol) and progesterone replacement cycle., (Copyright © 2024 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

The pathogenesis of endometriosis is a hotly debated topic, yet still cloaked in multiple layers of hypothetical theories. A recent report raises the possibility that bacterial infection, especially those of the genus Fusobacterium, may be the cause of endometriosis, at least in certain women. More importantly, the demonstration that treatment with broad-spectrum antibiotics significantly reduced the size of lesions in a mouse endometriosis model rekindles the hope for new non-hormonal treatments. The development of new therapies has been plagued by strings of unsuccessful clinical trials over the last two decades. Is this antibiotic therapy, a silver lining for the research and development of non-hormonal drugs for endometriosis?, (© The Author(s) 2024. 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.)

Fertility preservation for cancer has existed for three decades. The advent of highly effective oocyte cryopreservation by vitrification has paved the way for social fertility preservation. The options are discussed., Competing Interests: Declaration of Interests E.S. has nothing to disclose. S.S. has nothing to disclose. J.M.A. has nothing to disclose. D.D.Z. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the impact of paternal age on cumulative live birth rate in ART., Design: Retrospective single-center cohort study., Patients: All female patients aged 18-43 years and male patients aged 18-60 years, who performed their first ART cycle between January 2018 and December 2020, were included., Main Outcome Measures: The primary outcome, cumulative live birth rate (cLBR), was estimated following fresh or frozen embryo transfers issued from an ART cycle. Secondary outcomes included the cumulative pregnancy rate (cPR) and miscarriage rate. Subgroup analyzes were performed as follows: men <45 and ≥ 45; female <35, 35-38, and > 38 years., Results: A total of 2,358 couples were included in this study. The sperm quantity of male patients within both age groups was divided in two groups: normal and abnormal, which were found to be in significantly equal proportions. There were significantly fewer current smokers in the male group ≥45. The cPR was 0.5301 in the group <45 and 0.3111 in the group ≥45, with a p-value <0.001. Analysis according to the female age revealed that, in the female group >38, the cLBR rate was 0.26 for men <45 and 0.19 for men ≥45, with a p-value of 0.061. Additionally, the cPR was 0.34 in the male group <45 and 0.21 in the group ≥45, with a p-value <0.001. In the female group between 35 and 38 years of age, the cLBR was 0.44 in the male group <45 and 0.3 in the male group ≥45, with a p-value of 0.031. The cPR was 0.49 in the male group <45 and 0.34 in the group ≥45, p  = 0.036. Within the female group <35, we observed non-significant results. The miscarriage rate results were not significantly different for women ≤38., Conclusion: According to the results from our study, male age ≥ 45 has a significant impact on cumulative ART outcomes., 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 © 2024 Farabet, Pirtea, Benammar, De Ziegler, Marchiori, Vallée and Ayoubi.)

Importance: Although multiple mechanisms have been proposed to explain the infertility related to endometriosis, there are no conclusive data on the association of endometriosis with endometrial receptivity. The oocyte donation model in assisted reproduction technology (ART) cycles can clarify this issue., Objective: To explore the association of a history of endometriosis with ART outcomes in recipients of oocyte donation., Data Sources: In this systematic review and meta-analysis, electronic databases were searched from inception until August 31, 2023, using combinations of relevant keywords. Moreover, we retrieved data from the databases of the Society for Assisted Reproductive Technology (SART) in the US and the Human Fertilization and Embryology Authority (HFEA) in the United Kingdom., Study Selection: Observational studies were included if they investigated the impact of endometriosis on ART outcomes with donor oocytes., Data Extraction and Synthesis: Publicly available data related to ART from various sources were gathered, and a retrospective aggregate and nonaggregate analysis using registries of in vitro fertilization cycles with oocyte or embryo donation was conducted., Main Outcomes and Measures: The primary outcome was live birth rate (LBR) following oocyte donor cycles. The effect measures of comparisons between groups are presented as odds ratios (ORs) with a 95% CI., Results: This study analyzed 7212 oocyte donation cycles from 4 studies for the meta-analysis, along with 162 082 cycles from 2 registries (137 182 from SART and 24 900 from HFEA). No significant differences between the groups were observed in the meta-analysis of published data after adjusting for confounding factors (OR, 0.54; 95% CI, 0.19-1.57). A statistically significant lower LBR was identified in women with endometriosis when analyzing the aggregate data from SART and HFEA databases (OR, 0.89; 95% CI, 0.81-0.97)., Conclusions and Relevance: This study found a modest decrease in LBR among women with a history of endometriosis, although only results from the pooled analysis of registry data and not those from the meta-analysis reached statistical significance. These findings suggest that a marginal impairment of uterine receptivity may contribute to infertility mechanisms in women affected by endometriosis.

The improvements accomplished in assisted reproductive technology have emphasized more than ever the role played by chronological age, notably for predicting oocyte quality. Studies in cellular aging have directed research on telomere length measurements as possible markers of functional aging and, notably, female reproductive outcomes. Although further research is still needed, encouraging results are already available on the possibility that leucocyte telomere length may be a useful parameter for assessing reproductive potential in aging women., Competing Interests: Declaration of interests P.P. has nothing to disclose. D.L.K. has nothing to disclose. J.M.A. has nothing to disclose. D.D.Z. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

McCune-Albright syndrome (MAS) is a rare genetic disease affecting multiple organs, including endocrine tissues. This endocrinopathy is sometimes responsible for infertility, as it may induce an independent functioning of the ovaries leading to anovulatory cycles. This case report describes the infertility journey of a 22-year-old female who had early puberty and irregular periods with high estrogen and progesterone levels, low FSH and LH (on day 3 of her menstrual cycle), and a multi-cystic right ovary. She received several infertility treatments: initially in vitro oocyte maturation (IVM) followed by cyst transvaginal ultrasound-guided aspiration, all unsuccessful. A right hemi-ovariectomy was performed that eventually restored regular cycles and made it possible to perform ovarian stimulation (OS) and in vitro fertilization (IVF). Live birth was obtained after the first embryo transfer., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on the basis of clinicians' judgment., Objective: International experts in reproductive medicine met on July 1, 2022, in Lugano, Switzerland, to review the different facets of RIF and define the diagnosis and its appropriate management., Evidence Review: A systematic review without meta-analysis of studies published in English from January 2015 to May 2022., Findings: Data indicated that RIF has been largely overevaluated, overdiagnosed, and overtreated without sufficient critical assessment of its true nature. Our analyses show that true RIF is extremely uncommon-occurring in <5% of couples with infertility-and that reassurance and continued conventional therapies are warranted in most cases of assisted reproductive technology (ART) failure. Although the true biologic determinants of RIF may exist in a small subset of people with infertility, they elude the currently available tools for assessment. Without identification of the true underlying etiology(ies), it is reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid blastocyst transfers (or the equivalent number of unscreened embryo transfers, adjusted to the patient's age and corresponding euploidy rate). In addition, other factors should be ruled out that may contribute to her reduced odds of sustained implantation. In such cases, implantation failure should not be the only issue considered in case of ART failure because this may result from multiple other factors that are not necessarily repetitive or persistent. In reality, RIF impacting the probability of further ART success is a very rare occurrence., Conclusion: True RIF is extremely uncommon, occurring in <5% of couples with infertility. Reassurance and continued conventional therapies are warranted in most cases. It would seem reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid embryo transfers (or the equivalent number of unscreened embryos, adjusted to her age)., Relevance: Given the number of internationally recognized experts in the field present at the Lugano meeting 2022, our publication constitutes a consensus statement., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To gain insights into the technical feasibility of maternal spindle transfer (MST) applied in the context of repeated in vitro fertilization (IVF) failures for the treatment of idiopathic infertility., Design: A prospective pilot study., Setting: IVF center., Patient(s): Twenty-five infertile couples with multiple previous unsuccessful IVF cycles (range, 3-11), no previous pregnancy, and no history of mitochondrial DNA (mtDNA) disease participated. The study focused on women <40 years, with previous IVF attempts characterized by a pattern of low fertilization rates and/or impaired embryo development. Couples with severe male-factor infertility were not eligible. Oocyte donors with previous successful IVF outcomes were matched with patients according to standard practice., Intervention(s): We performed MST by transferring metaphase II spindles from the patients' oocytes into the previously enucleated donor oocytes, followed by intracytoplasmic sperm injection, in vitro embryo culture, blastocyst biopsy, and vitrification. Only euploid blastocysts were considered for embryo transfer., Main Outcome Measure(s): Outcome measures included oocyte fertilization, blastocyst development, clinical pregnancy and live birth, incidence of mitochondrial carryover and potential mtDNA reversal, as well as general health of the children born., Result(s): Twenty-eight MST cycles produced 6 children (19 embryo transfers, 7 clinical pregnancies). Pediatric follow-up of the children, performed at intervals from birth to 12-24 months of age, revealed their development to be unremarkable. DNA fingerprinting confirmed that the nuclear DNA of MST children was inherited from both parents, without any contribution from the oocyte donor. For 5 of the children, mtDNA was derived almost exclusively (>99%) from the donor. However, 1 child, who had similarly low mtDNA carryover (0.8%) at the blastocyst stage, showed an increase in the maternal mtDNA haplotype, accounting for 30% to 60% of the total at birth., Conclusion(s): This pilot study provides the first insights into the feasibility of applying MST for patients with idiopathic infertility and repeated IVF failures. Reconstructed oocytes produced embryos capable of implanting, developing to term and producing apparently healthy newborns/children. However, claims concerning the efficacy of MST with respect to infertility treatment would be premature considering the limitations of this study. Importantly, mtDNA reversal was detected in one child born after MST, a finding with possible implications for mitochondrial replacement therapies., Clinical Trial Registration Number: Pilot trial registry number, ISRCTN11455145. The date of registration: 20/02/2018. The date of enrolment of the first patients: 18/03/2018., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: D.d.Z. participates in a speakers’ bureau for IBSA. The other authors have no conflict of interest to disclose.

A narrative review of endometrial receptivity in adenomyosis and/or endometriosis revealed that this parameter is difficult to assess in natural conception because both disorders alter natural fertility. Recent data emanating from assisted reproductive technology have allowed the study of endometrial receptivity in women affected by adenomyosis and endometriosis. This has upended our views on the effects of these 2 disorders on embryo implantation. Today, the very existence of altered receptivity in assisted reproductive technology is questioned. In this context, we now know that frozen euploid blastocyst transfers in estradiol and progesterone cycles have unaltered outcomes in both adenomyosis and endometriosis., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Adenomyosis and endometriosis share a common origin as both of them result from the development of endometrial tissue outside the endometrium. Despite this, the 2 disorders were until recently considered as 2 different entities notably, because of their different epidemiology. Today, however, new findings regarding core similarities in pathophysiology and endometrial receptivity - not altered in assisted reproductive technology when using frozen embryo transfers - tend to reunite these 2 ailments as variants of 1 disorder., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To present different approaches used in the surgical management of diaphragmatic endometriosis using the Davinci Robotic system., Design: A video article presenting patient positioning, port placement, and surgical techniques used in robotic excision of diaphragmatic endometriosis with concomitant pelvic disease., Setting: Endometriosis center., Patient(s): Patients undergoing excision of diaphragmatic endometriosis., Intervention(s): Systematic robotic approach to excise diaphragmatic lesions depending on the depth of invasion., Main Outcome Measures(s): The advantages and disadvantages of the lithotomy and the lateral decubitus approach were reviewed. Ports placements are illustrated according to the chosen approach. Diaphragmatic peritoneal stripping, diaphragmatic shaving, and diaphragmatic excision are different techniques used according to the depth of invasion., Results(s): N/A., Conclusion(s): The choice of approach between the lithotomy position and the left lateral decubitus position depend on the extent of the diaphragmatic disease and the presence of concomitant pelvic lesions. Despite the lack of high-quality evidence, the advantages of the robotic system may improve the outcomes in such difficult cases in comparison with conventional laparoscopy., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.)