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Single embryo transfer (SET) is a technique used in assisted reproductive treatment (ART) that is used to promote singleton pregnancies. To date, there are five reported cases of dizygotic twin pregnancies with mothers who underwent SET. Here, we present a sixth case of a dichorionic, diamniotic twin pregnancy with sex discordance. The patient is a 34-year-old woman with unexplained secondary infertility who underwent in vitro fertilization (IVF) and frozen-thawed embryo transfer from a SET. The ultrasonographic images from the first and second trimester scans identified dichorionic, diamniotic twin gestations. The delivery was full term and postnatal genetic testing confirmed 46, XX, and 46, XY offspring. Pathology reports of the placental and membrane findings reported diamniotic, dichorionic twins. There was no zygosity testing conducted, thus it is unknown if the twins are monozygotic or dizygotic. Two possible etiologies for sex-discordant twins, in this case, are concurrent natural conception via breakthrough ovulation at the time of SET, or discordant postzygotic nondisjunction of a single embryo. Multiple gestations may still occur in the setting of SET and zygosity testing in these instances would better elucidate our understanding of this occurrence. Moreover, improved data on the zygosity of multiple gestations following SET may enhance patient counseling.

Uterus transplantation (UTx) is a novel type of transplantation to treat infertility in women with an absent or nonfunctioning uterus. The International Society of Uterus Transplantation (ISUTx) has developed a registry to monitor worldwide UTx activities while serving as a repository for specific research questions.The web-based registry has separate data fields for donor, recipient, surgeries, immunosuppression, rejections, pregnancies with live birth(s), and transplant hysterectomies. Data are prospectively registered.A total of 45 UTx procedures have been registered; the majority (78%) of those procedures were live donor (LD) transplants. Median age of the LDs, deceased donors, and recipients were 50 y (range 32-62), 38.5 y (19-57), and 29 y (22-38), respectively. The duration of LD surgery was approximately twice as long as the recipient surgery. Postoperative complications of any Clavien-Dindo grade were registered in 20% of LDs and 24% of recipients. Rejection episodes were more frequent (33%) early after transplantation (months 1-5) compared with later time points (months 6-10; 21%). Healthy neonates were delivered by 16 recipients, with 3 women giving birth twice. The total live birth rate per embryo transfer was 35.8%. Median length of pregnancy was 35 gestational weeks. Twelve uteri were removed without childbirth, with 9 transplant hysterectomies occurring during the initial 7 mo post-UTx.A mandatory registry is critical to determine quality and process improvement for any novel transplantation. This registry provides a detailed analysis of 45 UTx procedures performed worldwide with a thorough analysis of outcomes and complications.

Outpatient procedures and flexible staffing models have become prevalent within the ambulatory surgical and procedural spaces of reproductive endocrinology and infertility practice. High volumes of outpatients are treated daily by rotating nurses, surgeons, and anesthesia staff, often with the added layer of trainees present. "Teaming" can allow stable units and ad hoc groups to partner better for enhanced efficiency, effectiveness, and patient experience in routine procedural activities. These skills then can be parlayed into the rare moments of crisis to improve safety outcomes. Teaming concepts, applied in routine and acute scenarios, can optimize clinical operations, patient experience, and outcomes in our reproductive endocrinology and infertility ambulatory procedural and surgical spaces.

In this case, pre-operative planning is the key component to all three groups' thought process where the MRI findings are suggestive of an atypical leiomyoma. MIGS and GYN-Onc both recommend an endometrial biopsy to evaluate for leiomyosarcoma. Despite this being a very large transmural fibroid involving the endometrial cavity with suspicious MRI findings, all specialties agree that a laparoscopic approach was appropriate, with MIGS and REI focusing on the inevitability of needing to repair the endometrial defect and avoiding intrauterine adhesions. Further, in view of the patient's advanced age, both MIGS and REI recommend IVF and embryo banking shortly post-operatively now that her ovaries should be accessible and given that her uterus needs time to heal.

Objective The aim of this systematic review and meta-analysis was to perform an updated analysis of the literature in regard to the surgical management of minimal to mild endometriosis. This study evaluated women of reproductive age with superficial endometriosis to determine if the results of surgical excision compared with those of ablation in improved pain scores postoperatively. Data Sources The following databases were searched from inception to May 2020 for relevant studies: Cochrane Central Register of Controlled Trials, PubMed (MEDLINE), Ovid (MEDLINE), Scopus, and Web of Science. Methods of Study Selection From our literature search, a total of 2633 articles were identified and screened. Ultimately, 4 randomized controlled trials were selected and included in our systematic review. The combined total number of subjects was 346 from these 4 studies, with sample sizes ranging from 24 to 170 participants. Data from 3 of the included studies were able to be compared and analyzed for a meta-analysis. The primary outcome was reduction in the visual analog scale (VAS) score for endometriosis-associated pain (dysmenorrhea, dyschezia, and dyspareunia), with follow-up time ranging from 6 to 60 months postoperatively. Tabulation, Integration, and Results Data extracted from each study included the mean reduction in the VAS score from baseline. A random-effects model was used owing to significant heterogeneity across the studies. Statistical analyses were performed using Review Manager 5.3 software (Cochrane Collaboration, London, United Kingdom). The meta-analyses showed no significant differences between the excision and ablation groups in the mean reduction in VAS scores from baseline to 12 months postoperatively for dysmenorrhea (mean difference [MD] –0.03; 95% confidence interval [CI], –1.27 to 1.22; p = .97), dyschezia (MD 0.46; 95% CI, –1.09 to 2.02; p = .56), and dyspareunia (MD 0.10; 95% CI, –2.36 to 2.56; p = .94). In addition, there were no significant differences between the excision and ablation groups in mean VAS scores at the 12-month follow-up and beyond for dysmenorrhea (MD –0.11; 95% CI, –2.14 to 1.93; p = .92), dyschezia (MD 0.01; 95% CI, –0.70 to 0.72; p = .99), and dyspareunia (MD 0.34; 95% CI, –1.61 to 2.30; p = .73). Conclusion On the basis of the data from our systematic review and pooled meta-analysis, no significant difference between laparoscopic excision and ablation was noted in regard to improving pain from minimal to mild endometriosis. However, to make definitive conclusions on this topic, larger randomized controlled trials are needed with longer follow-up.

Ovarian tissue cryopreservation (OTC) is an accepted method of fertility preservation. However, OTC is not standardized and many variations exist in the freezing strategy, tissue processing, and surgical approach. In this pilot study, we used a sheep model to compare slow freezing versus vitrification techniques, as well as the feasibility of processing ovarian tissue into a hyaluronan suspension of small ovarian units. Twelve ovaries were harvested from six female ewes. Paired tissues from each animal were assigned to different treatments and underwent freezing, thawing, autotransplantation, and second-look surgery, for a total of 18 surgical procedures and 3 measured time points. Treatments included whole tissue strips versus gel suspension and slow freezing versus vitrification. At each of the time points, tissue viability was measured by immunohistochemical analysis of CD31 and cleaved caspase-3 (CCASP3). CD31 and CCASP3 expression levels were equivalent between slow freezing and vitrification, and between whole ovarian tissue strips and gel suspension of fragmented ovarian tissue, at all time points. These preliminary data using a sheep model suggest that ovarian tissue is robust and likely to be minimally affected by aggressive fragmentation using a hyaluronan suspension. Furthermore, we provide evidence in support of vitrification as a viable option in OTC. Hyaluronan suspension of ovarian cortical fragments is novel and may represent a desirable method for reimplantation of frozen-thawed ovarian tissue in patients where occult malignant cells are a concern.

Uterus transplantation is a nascent but growing field. To support this growth, the United States Uterus Transplant Consortium proposes guidelines for nomenclature related to operative technique, vascular anatomy, and donor, recipient, and offspring outcomes. In terms of anatomy, the group recommends reporting donor arterial inflow and recipient anastomotic site delivering inflow to the graft and offers standardization of the names for the 4 veins originating from the uterus because of current inconsistency in this particular nomenclature. Seven progressive stages with milestones of success are defined for reporting on uterus transplantation outcomes: (1) technical, (2) menstruation, (3) embryo implantation, (4) pregnancy, (5) delivery, (6) graft removal, and (7) long-term follow-up. The 3 primary metrics for success are recipient survival (as reported for other organ transplant recipients), graft survival, and uterus transplant live birth rate (defined as live birth per transplanted recipient). A number of secondary outcomes should also be reported, most of which capture stage-specific milestones, as well as data on graft failure. Outcome metrics for living donors include patient survival, survival free of operative intervention, and data on complications and hospitalizations. Finally, we make specific recommendations on follow-up for offspring born from uterine grafts, which includes specialty surveillance as well as collection and reporting of routine pediatric outcomes. The goal of standardization in reporting is to create consistency and improve the quality of evidence available on the efficacy and value of the procedure.

Endometriosis is a female disease which is defined as the presence of ectopic endometrial tissue and is dependent on estrogen for its survival in these ectopic locations. Expression of the ribosomal protein large P1 (RPLP1) is associated with cell proliferation and invasion in several pathologies, but a role in the pathophysiology of endometriosis has not been explored. In this study, we aimed to evaluate the expression and function of RPLP1 with respect to endometriosis pathophysiology. RPLP1 protein was localised by immunohistochemistry (IHC) in eutopic and ectopic tissue from 28 subjects with confirmed endometriosis and from 20 women without signs or symptoms of the disease, while transcript levels were evaluated by qRT-PCR in 77 endometriotic lesions and 55 matched eutopic endometrial biopsies, and protein expression was evaluated using western blotting in 20 of these matched samples. To evaluate the mechanism for enhanced lesion expression of RPLP1, an experimental murine model of endometriosis was used and RPLP1 expression was localized using IHC. In vitro studies using an endometriosis cell line coupled with shRNA knockdown was used to demonstrate its role in cell survival. Expression of RPLP1 mRNA and protein were significantly higher in ectopic lesion tissue compared to paired eutopic endometrium and immunohistochemical localisation revealed predominant localisation to epithelial cells. This pattern of lesion RPLP1 was recapitulated in mice with experimentally induced endometriosis. Stable knockdown of RPLP1 protein resulted in a significant decrease in cell survival in vitro. These studies reveal that RPLP1 is associated with cell proliferation and/or survival and may play a role in the pathophysiology of endometriosis.

Endometrial biopsy or curetting is indicated for postmenopausal women with abnormal uterine bleeding and/or thickened endometrium. Often, endometrial biopsy or curetting yields limited benign surface endometrium, which may indicate insufficient sampling. This study addresses the clinical outcome and subsequent pathologic diagnoses in postmenopausal women who received this initial diagnosis. Among a total of 370 endometrial biopsy or curetting between 2012 and 2015, 192 (52%) were diagnosed as limited benign surface endometrial epithelium. The women ranged in age from 55 to 91 yr old. Their clinical presentations mainly included postmenopausal bleeding, pelvic pain, and enlarged uterus. Primarily because the initial report was interpreted as "benign," 108 (57%) had no subsequent follow-up. Interestingly, women with an increased endometrial thickness were more likely to receive repeat evaluation. Among the 84 women who underwent follow-up endometrial sampling, 6 (7%) had hyperplasia with atypia or malignancy, 21 (25%) had a repeat diagnosis of limited surface sample, 4 (5%) had insufficient materials, and 53 (63%) had other benign findings. Among the subset of women who did receive subsequent follow-up, endometrial atypia or malignancies are more likely found in those with increased body mass index. In conclusion, a slight majority of women with postmenopausal bleeding and/or thickened endometrium had an initial limited surface endometrial sample. Most had no subsequent endometrial sampling. Among those with subsequent follow-up, the majority had benign findings. The study highlights the inconsistencies in adequacy criteria for endometrial sampling and the lack of standardization of subsequent management.

Importance Endometriomas are a unique and complex representation of the classic phenotypes of endometriosis. Associated symptoms, high recurrence rate, and multimodal approach represent ongoing challenges in the management of this chronic disease. Objective To review current literature regarding medical and surgical management of endometriomas. Evidence acquisition An extensive literature search including PubMed and Cochrane Library was performed. Review was performed using the following key words: "endometrioma," "cystectomy," "chronic pain," "infertility," "IVF," "menopause," "recurrence." All pertinent articles were assessed. The references of those articles were then reviewed, and additional publications were evaluated. Eligibility of the studies was first assessed on titles and abstracts. Full articles were then reviewed for all selected studies, and decision for final inclusion was made at that time. Conclusions and relevance Cystectomy of ovarian endometriomas has been the first-line treatment for management for many years because it provides improved pain relief, reduces recurrence rates, and was thought to be favorable in in vitro fertilization. However, a growing body of evidence is demonstrating benefit, or at least no harm, in expectant management for asymptomatic patients with small, stable endometriomas. Medical management is often very effective and appropriate first line. When surgical intervention is appropriate, careful ovarian cyst excision with goal of ovarian tissue preservation and treatment of additional endometriosis by a trained surgeon can provide the patient the best long-term outcome and preservation of ovarian tissue and function.

PURPOSE: To compare growth factor and cytokine profiles in the endometrial secretions of patients with and without endometriosis to determine whether a particular protein profile is predictive of the disease. METHODS: Patients undergoing laparoscopic gynecologic surgery for benign indications were recruited for this prospective cohort study. Prior to surgery, endometrial fluid was aspirated and multiplex immunoassay was used to quantify 7 cytokines and growth factors. During surgery, each patient was staged according to the ASRM staging system for endometriosis. Cytokines and growth factors were evaluated using the Mann-Whitney and Kruskal-Wallis tests. Combinations of cytokines were evaluated using logistic regression analysis, and ROC curves were generated to evaluate the predictive capacity of the assay. RESULTS: Endometrial secretions were analyzed from 60 patients. Nineteen had stage 3–4 endometriosis, 19 had stage 1–2 disease, and 22 had no endometriosis. There were no significant differences between controls and stage 1–2 endometriosis; however, levels of IL-1α and IL-6 were significantly increased in women with moderate-to-severe disease. A combination of IL-1α, IL-1β, and IL-6 in endometrial secretions predicts stage 3–4 endometriosis with an AUC of 0.78. A threshold value of 118 pg/mL yields a sensitivity of 75% and specificity of 70%. CONCLUSION: Aspiration of endometrial fluid is a safe and effective approach for evaluating the endometrial profile of women with endometriosis. Women with moderate-to-severe endometriosis demonstrate a distinct cytokine profile compared to controls. A combination of IL-1α, IL-1β, and IL-6 in the endometrial secretions is predictive of stage 3–4 endometriosis, but is not predictive of minimal-to-mild disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-020-01989-y.

To evaluate the general knowledge of female graduate students on reproductive aging and fertility preservation options, as well as to investigate the perceptions, personal beliefs, and desires regarding fertility and preservation modalities.A cross-sectional online survey study of female graduate students and medical trainees from academic institutions in Ohio was performed. Women were excluded if the online survey was incomplete or if they were 45 years.Analysis of 590 surveys was performed (response rate of 26.3%). Ninety-four percent (557/590) of subjects were between 20 and 35 years. Our respondents tended to be nulliparous (87%), married or in a relationship (51%) and interested in future fertility (77%). The reasons cited for delaying childbearing were multi-factorial, with career building noted most commonly (69%). Nearly 60% of women reported they would consider fertility preservation in the future; however, the majority (87%) cited two or more barriers. When asked about their desire for information on fertility preservation, 28% desired to receive education on their choices and 36% wanted their Ob/Gyn to discuss fertility preservation options. Women 30 years were significantly more likely to desire future fertility, want more fertility preservation education and consider pursuing fertility preservation in the future.Graduate-level women often delay childbearing for professional pursuits. This study demonstrates a need for increased fertility preservation awareness and education, especially by Ob/Gyn providers.

Endometriosis is a common and challenging condition of reproductive-aged women that carries a high individual and societal cost. The many molecular dissimilarities between endometriosis lesions and eutopic endometrium create difficulties in the development of new drug therapies and treatments. Surgery remains the gold standard for definitive diagnosis, but it must be weighed against the risks of surgical morbidity and potential decreases in ovarian reserve, especially in the case of endometriomas. Safe and effective surgical techniques are discussed within this article for various presentations of endometriosis. Medical therapy is suppressive rather than curative, and regimens that are long-term and affordable with minimal side effects are recommended. Recurrences are common and often rapid when medical therapy is discontinued. Endometriosis in the setting of infertility is reviewed and appropriate management is discussed, including when and whether surgery is warranted in this at-risk population. In patients with chronic pain, central sensitization and myofascial pain are integral components of a multidisciplinary approach. Endometriosis is associated with an increased risk of epithelial ovarian cancer; however, the risk is low and currently no preventive screening is recommended. Hormone therapy for symptomatic women with postsurgical menopause should not be delayed as a result of concerns for malignancy or recurrence of endometriosis.

Although women are inextricably involved in the study of germline editing, their interests have not been significantly represented in debates about the evolution of genome editing technology. Discussions have taken place about effects of germline editing on women as parents and members of families, but key discussions about women's health and well-being as patients and subjects are lacking. This neglect is due in part to restrictions on uterine transfer of modified human embryos, a boundary that has now been crossed. As a result, only scant discussion has taken place about safeguards needed to ensure that women who participate in germline modification research are not exposed to disproportionate risk in exchange for benefits they might expect for future offspring. This omission sets the stage for serious ethical implications for women and their families.

Objective To demonstrate techniques for successful donor-to-recipient vaginal anastomosis in uterine transplantation including illustration of a tension-free technique. Design This video uses live-action footage from surgery, detailed animations, and illustrations to review the step-by-step technique we use for vaginal anastomosis in uterine transplantation. Institutional Review Board approval was obtained for this experimental surgery. Setting Academic medical center. Patient(s) Patients undergoing uterine transplantation. Intervention(s) Preparation of recipient vagina with illustration of challenges and risk secondary to dense adhesions between bladder and neo-vagina. Use of surgical techniques. Key steps include appropriate preparation of both donor and recipient vaginal tissues and a tension-free closure with horizontal mattress stitches. Main Outcome Measure(s) Intraoperative techniques in the clinical research trial of uterine transplantation. Results Successful vaginal anastomosis in the uterine transplantation patient. Conclusion(s) This video provides a step-by-step guide to vaginal anastomosis in uterine transplantation patients. Our team has applied techniques from vaginal reconstructive surgery in an attempt to reduce the occurrence of postoperative vaginal strictures, with attention to planned donor and recipient anastomosis site tissue preparation and closure of the anastomosis using a tension-free suturing technique.

Uterus transplantation is the only known potential treatment for absolute uterine factor infertility. It offers a unique setting for the investigation of immunologic adaptations of pregnancy in the context of the pharmacologic-induced tolerance of solid organ transplants, thus providing valuable insights into the early maternal-fetal interface. Until recently, all live births resulting from uterus transplantation involved living donors, with only 1 prior birth from a deceased donor. The Cleveland Clinic clinical trial of uterus transplantation opened in 2015. In 2017, a 35 year old woman with congenital absence of the uterus was matched to a 24 year old parous deceased brain-dead donor. Transplantation of the uterus was performed with vaginal anastomosis and vascular anastomoses bilaterally from internal iliac vessels of the donor to the external iliac vessels of the recipient. Induction and maintenance immunosuppression were achieved and subsequently modified in anticipation of pregnancy 6 months after transplant. Prior to planned embryo transfer, ectocervical biopsy revealed ulceration and a significant diffuse, plasma cell-rich mixed inflammatory cell infiltrate, with histology interpreted as grade 3 rejection suspicious for an antibody-mediated component. Aggressive immunosuppressive regimen targeting both cellular and humoral rejection was initiated. After 3 months of treatment, there was no histologic evidence of rejection, and after 3 months from complete clearance of rejection, an uneventful embryo transfer was performed and a pregnancy was established. At 21 weeks, central placenta previa with accreta was diagnosed. A healthy neonate was delivered by cesarean hysterectomy at 34 weeks' gestation. In summary, this paper highlights the first live birth in North America resulting from a deceased donor uterus transplant. This achievement underscores the capacity of the transplanted uterus to recover from a severe, prolonged rejection and yet produce a viable neonate. This is the first delivery from our ongoing clinical trial in uterus transplantation, including the first reported incidence of severe mixed cellular/humoral rejection as well as the first reported placenta accreta.

This chapter overviews the history of deceased donor uterus transplantation and explores the major components of the medical evaluation of a deceased uterine donor. That includes obtaining the medical and surgical history, serological and microbiological evaluation, and preoperative imaging. Moreover, the challenges associated with obtaining consent from a deceased donor’s family will be discussed.

Fertility concerns are common in men and women of reproductive age, and primary care physicians are often the first line in addressing, assessing, and referring these patients. This article reviews the answers to questions patients often ask, and outlines a practical framework for the evaluation and management of the infertile couple. Up-to-date information is provided on available assisted reproductive technologies for the infertile couple, as well as preserving fertility in the setting of aging-related changes in the female reproductive system.

While uterus transplantation was once considered only a theoretical possibility for patients with uterine factor infertility, researchers have now developed methods of transplantation that have led to successful pregnancies with multiple children born to date. Because of the unique and significant nature of this type of research, it has been undertaken with collaboration not only with scientists and physicians but also with bioethicists, who paved the initial path for research of uterus transplantation to take place. As the science of uterus transplantation continues to advance, so too must the public dialogue among obstetrician/gynecologists, transplant surgeons, bioethicists, and other key stakeholders in defining the continued direction of research in addition to planning for the clinical implementation of uterus transplantation as a therapeutic option. Given the rapid advances in this field, the time has come to revisit the fundamental questions raised at the inception of uterus transplantation and, looking forward, determine the future of this approach given emerging data on the procedure's impact on individuals, families, and society.