Take it or leave it: oophorectomy at the time of benign hysterectomy.

PURPOSE OF REVIEW: Previous modeling data suggest ovarian conservation up to age 65 for women without adnexal disease and at average risk of ovarian cancer because of an increase in mortality associated with ovarian removal. Recent modeling data challenges this practice. This review of recent literature will update providers regarding consideration for oophorectomy at time of benign hysterectomy. RECENT FINDINGS: Oophorectomy at time of hysterectomy for women less than 50 years with estrogen supplementation and greater than 50 years without estrogen supplementation is not associated with increased mortality. SUMMARY: Although not associated with increased mortality, the decision to remove the ovaries at time of hysterectomy in women older than 50 years is nuanced and requires careful shared decision-making, considering unique patient factors.

Adenomyosis and fertility: does adenomyosis impact fertility and does treatment improve outcomes.

PURPOSE OF REVIEW: Adenomyosis has recently been associated with infertility. Relief of bleeding and pain has been demonstrated with medical and surgical therapy. Less is known about reproductive outcomes after treatment. RECENT FINDINGS: Imaging findings during infertility evaluation can be suggestive of adenomyosis without pathologic evaluation. Among women with infertility undergoing assisted reproductive technologies (ART), adenomyosis is associated with lower live birth rates and clinical pregnancy rates. Treatment with gonadotropin releasing hormone (GnRH) modulators prior to frozen embryo transfer may increase the live birth rate and clinical pregnancy rate among women with adenomyosis. Pregnancy has been documented following image-guided adenomyosis ablation; however, the reproductive impact is not well established. Pregnancy following excisional procedures appears to be well tolerated, although may carry a higher risk of uterine rupture compared with pregnancy following myomectomy. It is not clear if ablative therapy or resection increases pregnancy rates. SUMMARY: Adenomyosis is associated with lower embryo implantation rates and ongoing pregnancy rates. Adenomyotic changes in the uterus can be seen by ultrasound and MRI. GnRH modulators may be useful for women with adenomyosis undergoing ART. Additional prospective data is warranted to determine the optimal medical or surgical therapy for women with adenomyosis desiring conception.Video abstract Supplementary digital content, http://links.lww.com/COOG/A78.

A Systematic Review of Adenomyosis: It Is Time to Reassess What We Thought We Knew about the Disease.

OBJECTIVE: To summarize and update our current knowledge regarding adenomyosis diagnosis, prevalence, and symptoms. DATA SOURCES: Systematic review of PubMed between January 1972 and April 2020. Search strategy included: "adenomyosis [MeSH Terms] AND (endometriosis[MeSH Term OR prevalence study [MeSH Terms] OR dysmenorrhea[text word] OR prevalence[Text Word] OR young adults [Text Word] OR adolesce* [Text Word] OR symptoms[Text Word] OR imaging diagnosis [Text Word] OR pathology[Text Word]. METHODS OF STUDY SELECTION: Articles published in English that addressed adenomyosis and discussed prevalence, diagnosis, and symptoms were included. The included articles described pathology diagnosis, imaging, biopsy diagnosis, prevalence and age of onset, symptoms, and concomitant endometriosis. TABULATION, INTEGRATION, AND RESULTS: Sixteen articles were included in the qualitative analysis. The studies are heterogeneous when diagnosing adenomyosis with differing criteria, protocols, and patient populations. The prevalence estimates range from 20% to 88.8% in women who are symptomatic (average 30%-35%), with most diagnosed between the ages of 32 years and 38 years. The correlation between imaging and pathology continues to evolve. As imaging advances, newer studies report that younger women who are symptomatic are being diagnosed with adenomyosis on the basis of both magnetic resonance imaging and/or transvaginal ultrasound. High rates of concomitant endometriosis create challenges when discerning the etiology of pelvic pain. Symptoms that are historically attributed to endometriosis may actually be caused by adenomyosis. CONCLUSION: Adenomyosis remains a challenge to identify, assess, and research because of the lack of standardized diagnostic criteria, especially in women who wish to retain their uterus. As noninvasive diagnostics such as imaging and myometrial biopsies continue to improve, younger women with variable symptoms will likely create criteria for diagnosis with adenomyosis. The priority should be to create standardized histopathologic and imaging diagnoses to gain a deeper understanding of adenomyosis.

Novel Technology to Capture Objective Data from Patients' Recovery from Laparoscopic Endometriosis Surgery.

STUDY OBJECTIVE: To assess the feasibility of a noncontact radio sensor as an objective measurement tool to study postoperative recovery from endometriosis surgery. DESIGN: Prospective cohort pilot study. SETTING: Center for minimally invasive gynecologic surgery at an academically affiliated community hospital in conjunction with in-home monitoring. PATIENTS: Patients aged above 18 years who sleep independently and were scheduled to have laparoscopy for the diagnosis and treatment of suspected endometriosis. INTERVENTIONS: A wireless, noncontact sensor, Emerald, was installed in the subjects' home and used to capture physiologic signals without body contact. The device captured objective data about the patients' movement and sleep in their home for 5 weeks before surgery and approximately 5 weeks postoperatively. The subjects were concurrently asked to complete a daily pain assessment using a numeric rating scale and a free text survey about their daily symptoms. MEASUREMENTS AND MAIN RESULTS: Three women aged 23 years to 39 years and with mild to moderate endometriosis participated in the study. Emerald-derived sleep and wake times were contextualized and corroborated by select participant comments from retrospective surveys. In addition, self-reported pain levels and 1 sleep variable, sleep onset to deep sleep time, showed a significant (p <.01), positive correlation with next-day-pain scores in all 3 subjects: r = 0.45, 0.50, and 0.55. In other words, the longer it took the subject to go from sleep onset to deep sleep, the higher their pain score the following day. CONCLUSION: A patient's experience with pain is challenging to meaningfully quantify. This study highlights Emerald's unique ability to capture objective data in both preoperative functioning and postoperative recovery in an endometriosis population. The utility of this uniquely objective data for the clinician-patient relationship is just beginning to be explored.

Development and Application of the Metalloprotease Activity Multiplexed Bead-Based Immunoassay (MAMBI).

Metalloproteinases (MMPs) are zinc-dependent endopeptidases that cleave various proteins to regulate normal and diseased cellular functions, and as such, they play significant roles in human tissue development, homeostasis, and the pathogenesis of many diseases, including cancers, endometriosis, arthritis, etc. Most MMPs are produced as zymogenic latent enzymes that must be cleaved to activate their catalytic regions, and localized endogenous protein inhibitors further regulate activity. Accordingly, they operate within recursive networks to degrade extracellular matrix proteins and regulate cell signaling by cleaving growth factors and receptors at the cell surface and in the local pericellular environment. Thus, high-resolution information about the concentrations of specific active MMPs, revealing their intricate regulatory networks, may improve disease diagnosis and treatment. Here, we introduce a new and readily mastered method for measuring MMP activities in a multiplex fashion. We integrate aspects of activity-based enzyme labeling with commercial high-throughput, multiplexed protein quantification to yield the metalloproteinase activity multiplexed bead-based immunoassay (MAMBI). Assays of recombinant active MMP-1, -2, -3, -7, -8, -9, -12, and -13 establish the sensitivity and selectivity of MAMBI detection. Levels of active native MMPs are similarly characterized in conditioned cell culture medium, menstrual effluent, and uterine tissue. In a single MAMBI (5 µL), we achieve sensitivities equal to those from leading single-plex MMP activity detection strategies (e.g., 10-15 M for MMP-1). We also demonstrate high-throughput inhibitor screening via the MAMBI approach in complex, patient-derived samples.

Office Operative Hysteroscopy: An Update.

Hysteroscopy is considered the gold standard for the evaluation of intracavitary pathology in both premenopausal and postmenopausal patients associated with abnormal uterine bleeding, as well as for the evaluation of infertile patients with suspected cavity abnormalities. Office-based operative hysteroscopy allows patients to resume activities immediately and successfully integrates clinical practice into a "see and treat" modality, avoiding the added risks of anesthesia and the inconvenience of the operating room. For 2017, the Centers for Medicare and Medicaid Services has provided a substantial increase in reimbursement for a select number of office-based hysteroscopic procedures. This review provides an update on the indications, equipment, and procedures for office hysteroscopy, as well as the management of complications that may arise within an office-based practice.

Ultrasound guided core needle biopsy prior to thermo ablative treatment of uterine tumors: first results.

PURPOSE: This study aimed at evaluating the diagnostic yield for core needle biopsies of uterine fibroids before laparoscopic radiofrequency volumetric thermal ablation (RFVTA) with the aim of sonographic imaging. This study was in the context of a randomized, prospective, single-center, longitudinal comparative study in which RFVTA and laparoscopic myomectomy for symptomatic uterine fibroids were compared. METHODS: All patients of the RFVTA-arm received a core needle biopsy under the guidance of an intraoperative laparoscopic ultrasound system. The Tissue samples were observed histologically. RESULTS: 24 patients were included and received in the median 3.17 biopsies (range 2-7). 45.8% of the fibroids were intramural. In 92% uterine leiomyoma was detected, in 4% a cell rich leiomyoma and in 4% a smooth muscle tumor with uncertain malignant potential (STUMP). There were no complications caused by core needle biopsy. CONCLUSIONS: Ultrasound guided core needle biopsy can be used to receive a histological result before treating uterine fibroids with thermo surgical methods like RFVTA.

Contained tissue extraction using power morcellation: prospective evaluation of leakage parameters.

BACKGROUND: Safe tissue removal is a challenge for minimally invasive procedures such as myomectomy, supracervical hysterectomy, or total hysterectomy of a large uterine specimen. There is concern regarding disruption or dissemination of tissue during this process, which may be of particular significance in cases of undetected malignancy. Contained tissue extraction techniques have been developed in an effort to mitigate morcellation-related risks. OBJECTIVE: The objective of the study was to quantify perioperative outcomes of contained tissue extraction using power morcellation, specifically evaluating parameters of tissue or fluid leakage from within the containment system. STUDY DESIGN: This was a study including a multicenter prospective cohort of adult women who underwent minimally invasive hysterectomy or myomectomy using a contained power morcellation technique. Blue dye was applied to the tissue specimen prior to removal to help identify cases of fluid or tissue leakage from within the containment system. RESULTS: A total of 76 patients successfully underwent the contained power morcellation protocol. Mean time for the contained morcellation procedure was 30.2 minutes (±22.4). The mean hysterectomy specimen weight was 480.1 g (±359.1), and mean myomectomy specimen weight was 239.1 g (±229.7). The vast majority of patients (73.7%) were discharged home the same day of surgery. Final pathological diagnosis was benign in all cases. Spillage of dye or tissue was noted in 7 cases (9.2%), although containment bags were intact in each of these instances. CONCLUSION: Findings are consistent with prior work demonstrating the feasibility of contained tissue extraction; however, further refinement of this technique is warranted.

Multiplexed protease activity assay for low-volume clinical samples using droplet-based microfluidics and its application to endometriosis.

As principal degrading enzymes of the extracellular matrix, metalloproteinases (MPs) contribute to various pathologies and represent a family of promising drug targets and biomarker candidates. However, multiple proteases and endogenous inhibitors interact to govern MP activity, often leading to highly context-dependent protease function that unfortunately has impeded associated clinical utility. We present a method for rapidly assessing the activity of multiple specific proteases in small volumes (<20 µL) of complex biological fluids such as clinical samples that are available only in very limited amounts. It uses a droplet-based microfluidic platform that injects the sample into thousands of picoliter-scale droplets from a barcoded droplet library (DL) containing mixtures of unique, moderately selective FRET-based protease substrates and specific inhibitors and monitors hundreds of the reactions thus initiated simultaneously by tracking these droplets. Specific protease activities in the sample are then inferred from the reaction rates using a deconvolution technique, proteolytic activity matrix analysis (PrAMA). Using a nine-member DL with three inhibitors and four FRET substrates, we applied the method to the peritoneal fluid of subjects with and without the invasive disease endometriosis. The results showed clear and physiologically relevant differences with disease, in particular, decreased MMP-2 and ADAM-9 activities.

Does menstrual bleeding decrease after ablation of intramural myomas? A retrospective study.

STUDY OBJECTIVE: To evaluate the effect of radiofrequency volumetric thermal ablation (RFVTA) on menstrual bleeding in patients with intramural myomas. DESIGN: Retrospective analysis of a recently completed prospective trial of laparoscopic ultrasound-guided RFVTA in which 135 subjects had objectively measured heavy menstrual bleeding (≥160 to ≤500 mL) and confirmed submucosal, intramural, and subserosal myomas. We analyzed the pretreatment monthly menstrual blood loss as well as the response to treatment based on the types of myomas, specifically those subjects with only intramural myomas versus those with only submucosal myomas or those with both (Canadian Task Force classification II-2). SETTING: Outpatient hospital and private surgery centers. PATIENTS: One hundred thirty-five premenopausal symptomatic women (mean age: 42.4 ± 4.5 years) with uterine myomas and heavy menstrual bleeding confirmed by alkaline hematin analysis. INTERVENTIONS: Laparoscopic ultrasound-guided RFVTA. MEASUREMENTS AND MAIN RESULTS: Menstrual blood loss (MBL) at baseline and at 12 months after the procedure was quantified in 122 subjects with intramural myomas (including those that abut the endometrium, those that are within the myometrium, and those that extend from the serosa into the myometrium) and/or submucous myomas. Although 91.8% (112/122) of these subjects had 1 or more intramural myomas, submucous myomas were present in fewer than half of the subjects ([48.4%]). We identified 10 subjects who had submucous but no intramural myomas. This group had a significant (-45.1%) posttreatment decrease in monthly bleeding (95% confidence interval [CI], -78.0% to -12.2%; p = .013). In this same study, there were 63 subjects with intramural myomas and no submucosal myomas, and their posttreatment decrease in MBL of -31.8% was also clinically and statistically significant (95% CI, -41.4% to -22.2%; p<.001). Of those 63 subjects was a subset with intramural myomas (n = 27) without myomas abutting the endometrium or submucous myomas; this third set also resulted in a clinically and statistically significant reduction in MBL (-25.0% and -65.22 mL; 95% CI, -38.8% to -11.2%; p = .001). CONCLUSION: Although it has been known that the treatment of submucous myomas results in a reduction of MBL, this is the first study to show that radiofrequency ablative therapy for intramural myomas without a submucosal component will also result in a significant reduction in menstrual blood loss.

Laparoscopic supracervical hysterectomy (LSH) versus total laparoscopic hysterectomy (TLH): an implementation study in 1,952 patients with an analysis of risk factors for conversion to laparotomy and complications, and of procedure-specific re-operations.

PURPOSE: To compare laparoscopic supracervical hysterectomy (LSH) with total laparoscopic hysterectomy (TLH) with regard to relevant surgical parameters and risk factors of conversion to laparotomy and complications. METHODS: This prospective, open, single-center, interventional study included women with benign gynecologic disease who underwent standardized LSH or TLH. The techniques were compared for conversion rate and mean operating time, hemoglobin drop, hospital stay, and complication rates using descriptive statistics and standard non-parametric statistical tests. Risk factors of conversion and complications were identified by logistic regression analysis. RESULTS: During January 2003 to December 2010, 1,952 women [mean age (SD): 47.5 (7.2) years] underwent LSH [1,658 (84.9%)] or TLH [294 (15.1%)], mostly (>70%) for uterine fibroids. Significant differences in surgical parameters were observed for conversion rate (LSH/TLH: 2.6/6.5%), mean operating time [87 (34)/103 (36) min], hemoglobin drop [1.3 (0.8)/1.6 (1.0) g/dL], and hospital stay [4.3 (1.5)/4.9 (2.8) days]. Overall intraoperative (0.2/0.7%) and long-term (>6 weeks) post-operative (0.8/1.7%) complication rates did not differ significantly, but the short-term LSH complication rate was significantly lower (0.6 vs. 4.8%). Spotting (LSH, 0.2%) and vaginal cuff dehiscence (TLH, 0.7%) were long-term method-specific complications. Logistic regression showed that uterine weight and extensive adhesiolysis were significant factors for conversion while previous surgery, age, and BMI were not. Major risk factors of short-term complications were age, procedure (LSH/TLH), and extensive adhesions. CONCLUSIONS: Both procedures proved effective and were well tolerated. LSH performed better than TLH regarding most outcome measures. LSH is associated with very low rates of re-operation and spotting.

Infertility services integrated within the maternal health department of a public hospital in a low-income country, Rwanda.

Objective: To describe the initiation, integration, and costs of reduced-cost infertility services within the maternal health department of a public hospital in a low-income country. Design: Retrospective review of the clinical and laboratory components of patients undergoing in vitro fertilization (IVF) treatment in Rwanda from 2018 to 2020. Setting: Academic tertiary referral hospital in Rwanda. Patients: Patients seeking infertility services beyond the primary gynecological options. Interventions: The national government furnished facilities and personnel, and the Rwanda Infertility Initiative, an international nongovernmental organization, provided training, equipment, and materials. The incidence of retrieval, fertilization, embryo cleavage, transfer, and conception (observed until ultrasound verification of intrauterine pregnancy with fetal heartbeat) were analyzed. Cost calculations used the government-issued tariff specifying insurers' payments and patients' copayments with projected delivery rates using early literature. Main Outcome Measures: Assessment of functional clinical and laboratory infertility services and costs. Results: A total of 207 IVF cycles were initiated, 60 of which led to transfer of ≥1 high-grade embryo and 5 to ongoing pregnancies. The projected average cost per cycle was 1,521 USD. Using optimistic and conservative assumptions, the estimated costs per delivery for women <35 years were 4,540 and 5,156 USD, respectively. Conclusions: Reduced-cost infertility services were initiated and integrated within a maternal health department of a public hospital in a low-income country. This integration required commitment, collaboration, leadership, and a universal health financing system. Low-income countries, such as Rwanda, might consider infertility treatment and IVF for younger patients as part of an equitable and affordable health care benefit.

Organoid co-culture model of the human endometrium in a fully synthetic extracellular matrix enables the study of epithelial-stromal crosstalk.

BACKGROUND: The human endometrium undergoes recurring cycles of growth, differentiation, and breakdown in response to sex hormones. Dysregulation of epithelial-stromal communication during hormone-mediated signaling may be linked to myriad gynecological disorders for which treatments remain inadequate. Here, we describe a completely defined, synthetic extracellular matrix that enables co-culture of human endometrial epithelial and stromal cells in a manner that captures healthy and disease states across a simulated menstrual cycle. METHODS: We parsed cycle-dependent endometrial integrin expression and matrix composition to define candidate cell-matrix interaction cues for inclusion in a polyethylene glycol (PEG)-based hydrogel crosslinked with matrix metalloproteinase-labile peptides. We semi-empirically screened a parameter space of biophysical and molecular features representative of the endometrium to define compositions suitable for hormone-driven expansion and differentiation of epithelial organoids, stromal cells, and co-cultures of the two cell types. FINDINGS: Each cell type exhibited characteristic morphological and molecular responses to hormone changes when co-encapsulated in hydrogels tuned to a stiffness regime similar to the native tissue and functionalized with a collagen-derived adhesion peptide (GFOGER) and a fibronectin-derived peptide (PHSRN-K-RGD). Analysis of cell-cell crosstalk during interleukin 1B (IL1B)-induced inflammation revealed dysregulation of epithelial proliferation mediated by stromal cells. CONCLUSIONS: Altogether, we demonstrate the development of a fully synthetic matrix to sustain the dynamic changes of the endometrial microenvironment and support its applications to understand menstrual health and endometriotic diseases. FUNDING: This work was supported by The John and Karine Begg Foundation, the Manton Foundation, and NIH U01 (EB029132).

Women's preferences for minimally invasive incisions.

STUDY OBJECTIVE: To determine whether traditional, robotic, or single-site laparoscopic incisions are more appealing to women. DESIGN: Descriptive study using a survey (Canadian Task Force classification III). SETTING: Single-specialty referral-based gynecology practice. PATIENTS: All patients older than 18 years who came for care to the Newton-Wellesley Hospital Minimally Invasive Gynecological Surgery Center from April 2, 2010, to June 30, 2010. INTERVENTIONS: Three identical photos of an unscarred female abdomen were each marked with a black pen to indicate typical incision lengths and locations for robotic, single-site, and traditional laparoscopic surgery. Subjects were then asked to rank these incisions in order of preference. Additional demographic and surgical history questions were included in the survey. MEASUREMENTS AND MAIN RESULTS: Two-hundred fifty of 427 patients (58.5%) returned surveys, and of these, 241 completed critical survey elements. Preference for traditional laparoscopic incisions was 56.4% (95% confidence interval [CI], 50.1%-62.7%), for a single incision was 41.1% (95% CI, 34.8%-47.3%), and for robotic surgery was 2.5% (95% CI, 0.5%-4.5%). Two-sample test of proportion (Z test) showed the difference in preference for traditional over the other methods to be significant: p = .007 for a single incision and p <.001 for robotic surgery. Multivariatble analysis for factors influencing choice of single-site incision demonstrated that Latina/Hispanic ethnicity was the only significant factor (p = .02). CONCLUSION: Women prefer both single-site and traditional laparoscopic incisions over robotic procedures. Inasmuch as aesthetics are an important consideration for many women and clinical outcomes are similar, during the informed-consent procedure, location and length of incisions should be included in the discussion of risks, benefits, and alternatives.

Comparison of cytokines in the peritoneal fluid and conditioned medium of adolescents and adults with and without endometriosis.

PROBLEM: To compare inflammatory- and immune-associated peritoneal cytokines of adolescents and adults with and without endometriosis. METHODS OF STUDY: In a nested case-control study in multiple university-affiliated scientific centers, ten adolescents and thirteen adults with visually and histologically confirmed endometriosis (cases), thirteen adolescents with visually suspected endometriosis but indeterminate (seven patients) or negative (six patients) histology, and fifteen adults undergoing surgery for non-malignant gynecologic disease without endometriosis (controls) underwent laparoscopic aspiration of peritoneal fluid (PF), from which PF and conditioned medium (CM) cytokine levels were assayed. RESULTS: Compared to adults with endometriosis, MCP-3, IL-12p40, MIP-1ß, and IL-15 were significantly higher among adolescents with endometriosis, while TNF-ß and CTACK were lower among adolescents. These differences were similar comparing adolescents with endometriosis to adult controls except for MIP-1ß, which was not statistically different. MIP-1ß was, however, the only cytokine observed to differ between adult cases and controls. There were no significant differences in CM cytokines among the three groups. Results were similar when analyses were restricted to samples collected (a) during menstrual cycle days 1-10, (b) from patients unexposed to exogenous hormones, or (c) from all adolescents despite presence or absence of histologic endometriosis. CONCLUSION: Biologically relevant and statistically significant differences in six PF cytokines were observed and suggest a more pro-invasion cytokine profile among adolescents with endometriosis. Adolescents with endometriosis have unique peritoneal cytokine profiles and molecular behavior when compared to adults with and without endometriosis.

Hysteroscopy and why macroscopic uterine factors matter for fertility.

For humans, the uterus is their first home. Accurate evaluation and effective therapy are central to optimizing the conditions for implantation and sustained pregnancy. For macroscopic intracavitary disease, hysteroscopy remains the gold standard for diagnosis and treatment. We review the role of hysteroscopy before fertility therapies. We also address intracavitary pathologies and their relevance to procreative outcomes. Controversies in the literature are noted and clarified, and trends in the field of hysteroscopy are identified regarding how they will influence the future of reproductive care and women's health.

Peritoneal fluid cytokines related to endometriosis in patients evaluated for infertility.

OBJECTIVE: Our aim was to characterize peritoneal cytokine profiles in patients with infertility, with and without endometriosis, to illuminate potential differences in immune profiles that may reflect mechanistic differences between these two patient populations. DESIGN: Cross-sectional study. SETTING: University hospital and research center. PATIENT(S): Women undergoing laparoscopy for infertility investigation (n = 107). INTERVENTION(S): Peritoneal fluid was collected during surgery. Clinical characteristics were registered preoperatively. MAIN OUTCOME MEASURE(S): We determined the concentration of 48 different cytokines from the peritoneal fluid with multiplex immunoassays. Associations between cytokines and clinical findings were assessed with logistic regression and partial least squares discriminant analyses (PLS-DA). RESULT(S): Concentrations of SCGF-ß, IL-8, HGF, and MCP-1 were significantly higher, while IL-13 was significantly lower in the endometriosis group compared with the group without endometriosis. Multiple stepwise logistic regression identified a combination of SCGF-ß, IL-13, and G-CSF concentrations that predicted the presence of endometriosis with 86% sensitivity and 67% specificity. PLS-DA identified a class of 11 cytokines (SCGF-ß, HGF, IL-13, MCP-1, CTACK, MCP-3, M-CSF, LIF, IL-5, IL-9, and IFN-a2) that were more characteristic of endometriosis than nonendometriosis patients. CONCLUSION(S): By combining univariate and multivariate analyses, profiles of cytokines more likely to be enriched or depleted in infertility patients with endometriosis compared with those without endometriosis were identified. These findings may inform future analyses of pathophysiological mechanisms of endometriosis in infertile patients, including dysregulated Th1/Th2 response and mobilization and proliferation of hematopoietic stem cells.